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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2</title><author><name sortKey="Orr, Nick" sort="Orr, Nick" uniqKey="Orr N" first="Nick" last="Orr">Nick Orr</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dudbridge, Frank" sort="Dudbridge, Frank" uniqKey="Dudbridge F" first="Frank" last="Dudbridge">Frank Dudbridge</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Dryden, Nicola" sort="Dryden, Nicola" uniqKey="Dryden N" first="Nicola" last="Dryden">Nicola Dryden</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Maguire, Sarah" sort="Maguire, Sarah" uniqKey="Maguire S" first="Sarah" last="Maguire">Sarah Maguire</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Novo, Daniela" sort="Novo, Daniela" uniqKey="Novo D" first="Daniela" last="Novo">Daniela Novo</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Perrakis, Eleni" sort="Perrakis, Eleni" uniqKey="Perrakis E" first="Eleni" last="Perrakis">Eleni Perrakis</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Johnson, Nichola" sort="Johnson, Nichola" uniqKey="Johnson N" first="Nichola" last="Johnson">Nichola Johnson</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ghoussaini, Maya" sort="Ghoussaini, Maya" uniqKey="Ghoussaini M" first="Maya" last="Ghoussaini">Maya Ghoussaini</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation><nlm:aff id="af8"><addr-line>Department of Pathology</addr-line>,<institution>The University of Melbourne</institution>,<addr-line>Melbourne, VIC 3010</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Apicella, Carmel" sort="Apicella, Carmel" uniqKey="Apicella C" first="Carmel" last="Apicella">Carmel Apicella</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation></author><author><name sortKey="Stone, Jennifer" sort="Stone, Jennifer" uniqKey="Stone J" first="Jennifer" last="Stone">Jennifer Stone</name><affiliation><nlm:aff id="af9"><addr-line>Centre for Genetic Origins of Health and Disease</addr-line>,<institution>University of Western Australia</institution>,<addr-line>Perth, WA</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Marjanka K" sort="Schmidt, Marjanka K" uniqKey="Schmidt M" first="Marjanka K." last="Schmidt">Marjanka K. Schmidt</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Broeks, Annegien" sort="Broeks, Annegien" uniqKey="Broeks A" first="Annegien" last="Broeks">Annegien Broeks</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Van T Veer, Laura J" sort="Van T Veer, Laura J" uniqKey="Van T Veer L" first="Laura J." last="Van'T Veer">Laura J. Van'T Veer</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Hogervorst, Frans B" sort="Hogervorst, Frans B" uniqKey="Hogervorst F" first="Frans B." last="Hogervorst">Frans B. Hogervorst</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Fasching, Peter A" sort="Fasching, Peter A" uniqKey="Fasching P" first="Peter A." last="Fasching">Peter A. Fasching</name><affiliation><nlm:aff wicri:cut=" and" id="af11"><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af13"><addr-line>David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology</addr-line>,<institution>University of California at Los Angeles</institution>,<addr-line>Los Angeles, CA 90095</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Haeberle, Lothar" sort="Haeberle, Lothar" uniqKey="Haeberle L" first="Lothar" last="Haeberle">Lothar Haeberle</name><affiliation><nlm:aff wicri:cut=" and" id="af11"><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ekici, Arif B" sort="Ekici, Arif B" uniqKey="Ekici A" first="Arif B." last="Ekici">Arif B. Ekici</name><affiliation><nlm:aff id="af12"><addr-line>Institute of Human Genetics, University Hospital Erlangen</addr-line>,<institution>Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN</institution>,<addr-line>91054 Erlangen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Beckmann, Matthias W" sort="Beckmann, Matthias W" uniqKey="Beckmann M" first="Matthias W." last="Beckmann">Matthias W. Beckmann</name><affiliation><nlm:aff wicri:cut=" and" id="af11"><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gibson, Lorna" sort="Gibson, Lorna" uniqKey="Gibson L" first="Lorna" last="Gibson">Lorna Gibson</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Aitken, Zoe" sort="Aitken, Zoe" uniqKey="Aitken Z" first="Zoe" last="Aitken">Zoe Aitken</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Warren, Helen" sort="Warren, Helen" uniqKey="Warren H" first="Helen" last="Warren">Helen Warren</name><affiliation><nlm:aff wicri:cut=" and" id="af14"><addr-line>Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af15"><addr-line>NIHR Barts Cardiovascular Biomedical Research Unit</addr-line>,<institution>Queen Mary University of London</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Sawyer, Elinor" sort="Sawyer, Elinor" uniqKey="Sawyer E" first="Elinor" last="Sawyer">Elinor Sawyer</name><affiliation><nlm:aff id="af16"><addr-line>Division of Cancer Studies</addr-line>,<institution>Kings College London, Guy's Hospital</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Tomlinson, Ian" sort="Tomlinson, Ian" uniqKey="Tomlinson I" first="Ian" last="Tomlinson">Ian Tomlinson</name><affiliation><nlm:aff id="af17"><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre</addr-line>,<institution>University of Oxford</institution>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Kerin, Michael J" sort="Kerin, Michael J" uniqKey="Kerin M" first="Michael J." last="Kerin">Michael J. Kerin</name><affiliation><nlm:aff id="af18"><addr-line>Clinical Science Institute</addr-line>,<institution>University Hospital Galway</institution>,<addr-line>Galway</addr-line>,<country>Ireland</country>,</nlm:aff></affiliation></author><author><name sortKey="Miller, Nicola" sort="Miller, Nicola" uniqKey="Miller N" first="Nicola" last="Miller">Nicola Miller</name><affiliation><nlm:aff id="af18"><addr-line>Clinical Science Institute</addr-line>,<institution>University Hospital Galway</institution>,<addr-line>Galway</addr-line>,<country>Ireland</country>,</nlm:aff></affiliation></author><author><name sortKey="Burwinkel, Barbara" sort="Burwinkel, Barbara" uniqKey="Burwinkel B" first="Barbara" last="Burwinkel">Barbara Burwinkel</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af21"><addr-line>Molecular Epidemiology Group</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Marme, Frederik" sort="Marme, Frederik" uniqKey="Marme F" first="Frederik" last="Marme">Frederik Marme</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af20"><addr-line>National Center for Tumor Diseases</addr-line>,<institution>University of Heidelberg</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Schneeweiss, Andreas" sort="Schneeweiss, Andreas" uniqKey="Schneeweiss A" first="Andreas" last="Schneeweiss">Andreas Schneeweiss</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af20"><addr-line>National Center for Tumor Diseases</addr-line>,<institution>University of Heidelberg</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Sohn, Chistof" sort="Sohn, Chistof" uniqKey="Sohn C" first="Chistof" last="Sohn">Chistof Sohn</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Guenel, Pascal" sort="Guenel, Pascal" uniqKey="Guenel P" first="Pascal" last="Guénel">Pascal Guénel</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Truong, Therese" sort="Truong, Therese" uniqKey="Truong T" first="Thérèse" last="Truong">Thérèse Truong</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Cordina Duverger, Emilie" sort="Cordina Duverger, Emilie" uniqKey="Cordina Duverger E" first="Emilie" last="Cordina-Duverger">Emilie Cordina-Duverger</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Sanchez, Marie" sort="Sanchez, Marie" uniqKey="Sanchez M" first="Marie" last="Sanchez">Marie Sanchez</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Bojesen, Stig E" sort="Bojesen, Stig E" uniqKey="Bojesen S" first="Stig E." last="Bojesen">Stig E. Bojesen</name><affiliation><nlm:aff wicri:cut=" and" id="af24"><addr-line>Copenhagen General Population Study</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af25"><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Nordestgaard, B Rge G" sort="Nordestgaard, B Rge G" uniqKey="Nordestgaard B" first="B Rge G." last="Nordestgaard">B Rge G. Nordestgaard</name><affiliation><nlm:aff wicri:cut=" and" id="af24"><addr-line>Copenhagen General Population Study</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af25"><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Nielsen, Sune F" sort="Nielsen, Sune F" uniqKey="Nielsen S" first="Sune F." last="Nielsen">Sune F. Nielsen</name><affiliation><nlm:aff wicri:cut=" and" id="af24"><addr-line>Copenhagen General Population Study</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af25"><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Flyger, Henrik" sort="Flyger, Henrik" uniqKey="Flyger H" first="Henrik" last="Flyger">Henrik Flyger</name><affiliation><nlm:aff id="af26"><addr-line>Department of Breast Surgery</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>Copenhagen</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Benitez, Javier" sort="Benitez, Javier" uniqKey="Benitez J" first="Javier" last="Benitez">Javier Benitez</name><affiliation><nlm:aff id="af27"><addr-line>Human Genetics Group, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>28029 Madrid</addr-line>,<country>Spain</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af28"><institution>Centro de Investigación en Red de Enfermedades Raras (CIBERER)</institution>,<addr-line>46010 Valencia</addr-line>,<country>Spain</country>,</nlm:aff></affiliation></author><author><name sortKey="Zamora, Maria Pilar" sort="Zamora, Maria Pilar" uniqKey="Zamora M" first="Maria Pilar" last="Zamora">Maria Pilar Zamora</name><affiliation><nlm:aff id="af29"><addr-line>Servicio de Oncología Médica</addr-line>,<institution>Hospital Universitario La Paz</institution>,<addr-line>28046 Madrid</addr-line>,<country>Spain</country>,</nlm:aff></affiliation></author><author><name sortKey="Arias Perez, Jose Ignacio" sort="Arias Perez, Jose Ignacio" uniqKey="Arias Perez J" first="Jose Ignacio" last="Arias Perez">Jose Ignacio Arias Perez</name><affiliation><nlm:aff wicri:cut=" and" id="af30"><addr-line>Servicio de Cirugía General y Especialidades</addr-line></nlm:aff></affiliation></author><author><name sortKey="Menendez, Primitiva" sort="Menendez, Primitiva" uniqKey="Menendez P" first="Primitiva" last="Menéndez">Primitiva Menéndez</name><affiliation><nlm:aff id="af31"><addr-line>Servicio de Anatomía Patológica</addr-line>,<institution>Hospital Monte Naranco</institution>,<addr-line>33012 Oviedo</addr-line>,<country>Spain</country>,</nlm:aff></affiliation></author><author><name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name><affiliation><nlm:aff id="af32"><addr-line>Department of Epidemiology</addr-line>,<institution>University of California Irvine</institution>,<addr-line>Irvine, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Neuhausen, Susan L" sort="Neuhausen, Susan L" uniqKey="Neuhausen S" first="Susan L." last="Neuhausen">Susan L. Neuhausen</name><affiliation><nlm:aff id="af33"><institution>Beckman Research Institute of City of Hope</institution>,<addr-line>Duarte, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation><nlm:aff id="af34"><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Dieffenbach, Aida Karina" sort="Dieffenbach, Aida Karina" uniqKey="Dieffenbach A" first="Aida Karina" last="Dieffenbach">Aida Karina Dieffenbach</name><affiliation><nlm:aff id="af34"><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Arndt, Volker" sort="Arndt, Volker" uniqKey="Arndt V" first="Volker" last="Arndt">Volker Arndt</name><affiliation><nlm:aff id="af34"><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Stegmaier, Christa" sort="Stegmaier, Christa" uniqKey="Stegmaier C" first="Christa" last="Stegmaier">Christa Stegmaier</name><affiliation><nlm:aff id="af38"><institution>Saarland Cancer Registry</institution>,<addr-line>Saarbrücken</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Hamann, Ute" sort="Hamann, Ute" uniqKey="Hamann U" first="Ute" last="Hamann">Ute Hamann</name><affiliation><nlm:aff wicri:cut=" and" id="af36"><addr-line>Molecular Genetics of Breast Cancer</addr-line></nlm:aff></affiliation></author><author><name sortKey="Brauch, Hiltrud" sort="Brauch, Hiltrud" uniqKey="Brauch H" first="Hiltrud" last="Brauch">Hiltrud Brauch</name><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff id="af39"><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af40"><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Justenhoven, Christina" sort="Justenhoven, Christina" uniqKey="Justenhoven C" first="Christina" last="Justenhoven">Christina Justenhoven</name><affiliation><nlm:aff id="af39"><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af40"><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Bruning, Thomas" sort="Bruning, Thomas" uniqKey="Bruning T" first="Thomas" last="Brüning">Thomas Brüning</name><affiliation><nlm:aff id="af41"><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr—University Bochum (IPA)</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Ko, Yon Dschun" sort="Ko, Yon Dschun" uniqKey="Ko Y" first="Yon-Dschun" last="Ko">Yon-Dschun Ko</name><affiliation><nlm:aff id="af42"><addr-line>Department of Internal Medicine</addr-line>,<institution>Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af36"><addr-line>Molecular Genetics of Breast Cancer</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af39"><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af40"><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af41"><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr—University Bochum (IPA)</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af42"><addr-line>Department of Internal Medicine</addr-line>,<institution>Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af43"><addr-line>Institute of Pathology</addr-line>,<institution>Medical Faculty of the University of Bonn</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af44"><addr-line>Institute of Occupational Medicine and Maritime Medicine</addr-line>,<institution>University Medical Center Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name><affiliation><nlm:aff id="af45"><addr-line>Department of Obstetrics and Gynecology</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Aittom Ki, Kristiina" sort="Aittom Ki, Kristiina" uniqKey="Aittom Ki K" first="Kristiina" last="Aittom Ki">Kristiina Aittom Ki</name><affiliation><nlm:aff wicri:cut=" and" id="af46"><addr-line>Department of Clinical Genetics</addr-line></nlm:aff></affiliation></author><author><name sortKey="Blomqvist, Carl" sort="Blomqvist, Carl" uniqKey="Blomqvist C" first="Carl" last="Blomqvist">Carl Blomqvist</name><affiliation><nlm:aff id="af47"><addr-line>Department of Oncology</addr-line>,<institution>University of Helsinki and Helsinki University Hospital</institution>,<addr-line>Helsinki</addr-line>,<country>Finland</country>,</nlm:aff></affiliation></author><author><name sortKey="Khan, Sofia" sort="Khan, Sofia" uniqKey="Khan S" first="Sofia" last="Khan">Sofia Khan</name><affiliation><nlm:aff id="af45"><addr-line>Department of Obstetrics and Gynecology</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Bogdanova, Natalia" sort="Bogdanova, Natalia" uniqKey="Bogdanova N" first="Natalia" last="Bogdanova">Natalia Bogdanova</name><affiliation><nlm:aff wicri:cut=" and" id="af48"><addr-line>Department of Radiation Oncology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af49"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Hannover Medical School</institution>,<addr-line>Hannover</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Dork, Thilo" sort="Dork, Thilo" uniqKey="Dork T" first="Thilo" last="Dörk">Thilo Dörk</name><affiliation><nlm:aff id="af49"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Hannover Medical School</institution>,<addr-line>Hannover</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Lindblom, Annika" sort="Lindblom, Annika" uniqKey="Lindblom A" first="Annika" last="Lindblom">Annika Lindblom</name><affiliation><nlm:aff wicri:cut=" and" id="af50"><addr-line>Department of Molecular Medicine and Surgery</addr-line></nlm:aff></affiliation></author><author><name sortKey="Margolin, Sara" sort="Margolin, Sara" uniqKey="Margolin S" first="Sara" last="Margolin">Sara Margolin</name><affiliation><nlm:aff id="af51"><addr-line>Department of Oncology-Pathology</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Mannermaa, Arto" sort="Mannermaa, Arto" uniqKey="Mannermaa A" first="Arto" last="Mannermaa">Arto Mannermaa</name><affiliation><nlm:aff wicri:cut=" and" id="af52"><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af54"><addr-line>Imaging Center, Department of Clinical Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kataja, Vesa" sort="Kataja, Vesa" uniqKey="Kataja V" first="Vesa" last="Kataja">Vesa Kataja</name><affiliation><nlm:aff id="af53"><addr-line>School of Medicine, Institute of Clinical Medicine, Oncology</addr-line>,<institution>University of Eastern Finland</institution>,<addr-line>Kuopio</addr-line>,<country>Finland</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af55"><addr-line>Biocenter Kuopio, Cancer Center of Eastern Finland</addr-line>,<institution>Kuopio University Hospital</institution>,<addr-line>Kuopio</addr-line>,<country>Finland</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af56"><addr-line>Central Finland Health Care District</addr-line>,<institution>Jyväskylä Central Hospital</institution>,<addr-line>Jyväskylä</addr-line>,<country>Finland</country>,</nlm:aff></affiliation></author><author><name sortKey="Kosma, Veli Matti" sort="Kosma, Veli Matti" uniqKey="Kosma V" first="Veli-Matti" last="Kosma">Veli-Matti Kosma</name><affiliation><nlm:aff wicri:cut=" and" id="af52"><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af54"><addr-line>Imaging Center, Department of Clinical Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hartikainen, Jaana M" sort="Hartikainen, Jaana M" uniqKey="Hartikainen J" first="Jaana M." last="Hartikainen">Jaana M. Hartikainen</name><affiliation><nlm:aff wicri:cut=" and" id="af52"><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af54"><addr-line>Imaging Center, Department of Clinical Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name><affiliation><nlm:aff id="af57"><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name><affiliation><nlm:aff id="af57"><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af58"><institution>Peter MacCallum Cancer Center</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af57"><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af58"><institution>Peter MacCallum Cancer Center</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Lambrechts, Diether" sort="Lambrechts, Diether" uniqKey="Lambrechts D" first="Diether" last="Lambrechts">Diether Lambrechts</name><affiliation><nlm:aff id="af59"><addr-line>Vesalius Research Center (VRC)</addr-line>,<institution>VIB</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af60"><addr-line>Laboratory for Translational Genetics, Department of Oncology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Moisse, Matthieu" sort="Moisse, Matthieu" uniqKey="Moisse M" first="Matthieu" last="Moisse">Matthieu Moisse</name><affiliation><nlm:aff id="af59"><addr-line>Vesalius Research Center (VRC)</addr-line>,<institution>VIB</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af60"><addr-line>Laboratory for Translational Genetics, Department of Oncology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Floris, Guiseppe" sort="Floris, Guiseppe" uniqKey="Floris G" first="Guiseppe" last="Floris">Guiseppe Floris</name><affiliation><nlm:aff id="af61"><institution>University Hospital Gasthuisberg</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Beuselinck, Benoit" sort="Beuselinck, Benoit" uniqKey="Beuselinck B" first="Benoit" last="Beuselinck">Benoit Beuselinck</name><affiliation><nlm:aff id="af61"><institution>University Hospital Gasthuisberg</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name><affiliation><nlm:aff id="af37"><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name><affiliation><nlm:aff id="af37"><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Seibold, Petra" sort="Seibold, Petra" uniqKey="Seibold P" first="Petra" last="Seibold">Petra Seibold</name><affiliation><nlm:aff id="af37"><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Flesch Janys, Dieter" sort="Flesch Janys, Dieter" uniqKey="Flesch Janys D" first="Dieter" last="Flesch-Janys">Dieter Flesch-Janys</name><affiliation><nlm:aff wicri:cut=" and" id="af62"><addr-line>Department of Cancer Epidemiology/Clinical Cancer Registry</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af63"><addr-line>Institute for Medical Biometrics and Epidemiology</addr-line>,<institution>University Clinic Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Radice, Paolo" sort="Radice, Paolo" uniqKey="Radice P" first="Paolo" last="Radice">Paolo Radice</name><affiliation><nlm:aff wicri:cut=" and" id="af64"><addr-line>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine</addr-line></nlm:aff></affiliation></author><author><name sortKey="Peterlongo, Paolo" sort="Peterlongo, Paolo" uniqKey="Peterlongo P" first="Paolo" last="Peterlongo">Paolo Peterlongo</name><affiliation><nlm:aff id="af66"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation></author><author><name sortKey="Peissel, Bernard" sort="Peissel, Bernard" uniqKey="Peissel B" first="Bernard" last="Peissel">Bernard Peissel</name><affiliation><nlm:aff id="af65"><addr-line>Unit of Medical Genetics, Department of Preventive and Predictive Medicine</addr-line>,<institution>Fondazione IRCCS Istituto Nazionale dei Tumori (INT)</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation></author><author><name sortKey="Pensotti, Valeria" sort="Pensotti, Valeria" uniqKey="Pensotti V" first="Valeria" last="Pensotti">Valeria Pensotti</name><affiliation><nlm:aff id="af66"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af67"><institution>Cogentech Cancer Genetic Test Laboratory</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name><affiliation><nlm:aff wicri:cut=" and" id="af68"><addr-line>Department of Laboratory Medicine and Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Olson, Janet E" sort="Olson, Janet E" uniqKey="Olson J" first="Janet E." last="Olson">Janet E. Olson</name><affiliation><nlm:aff id="af69"><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Slettedahl, Seth" sort="Slettedahl, Seth" uniqKey="Slettedahl S" first="Seth" last="Slettedahl">Seth Slettedahl</name><affiliation><nlm:aff id="af69"><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Vachon, Celine" sort="Vachon, Celine" uniqKey="Vachon C" first="Celine" last="Vachon">Celine Vachon</name><affiliation><nlm:aff id="af69"><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af70"><addr-line>Cancer Epidemiology Centre</addr-line>,<institution>Cancer Council Victoria</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Milne, Roger L" sort="Milne, Roger L" uniqKey="Milne R" first="Roger L." last="Milne">Roger L. Milne</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af70"><addr-line>Cancer Epidemiology Centre</addr-line>,<institution>Cancer Council Victoria</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Mclean, Catriona" sort="Mclean, Catriona" uniqKey="Mclean C" first="Catriona" last="Mclean">Catriona Mclean</name><affiliation><nlm:aff id="af71"><addr-line>Anatomical Pathology</addr-line>,<institution>The Alfred Hospital</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A." last="Haiman">Christopher A. Haiman</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Henderson, Brian E" sort="Henderson, Brian E" uniqKey="Henderson B" first="Brian E." last="Henderson">Brian E. Henderson</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Schumacher, Fredrick" sort="Schumacher, Fredrick" uniqKey="Schumacher F" first="Fredrick" last="Schumacher">Fredrick Schumacher</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name><affiliation><nlm:aff id="af73"><addr-line>Epidemiology Program, Cancer Research Center</addr-line>,<institution>University of Hawaii</institution>,<addr-line>Honolulu, HI</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Simard, Jacques" sort="Simard, Jacques" uniqKey="Simard J" first="Jacques" last="Simard">Jacques Simard</name><affiliation><nlm:aff id="af74"><addr-line>Cancer Genomics Laboratory</addr-line>,<institution>Centre Hospitalier Universitaire de Québec Research Center and Laval University</institution>,<addr-line>Quebec City, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Goldberg, Mark S" sort="Goldberg, Mark S" uniqKey="Goldberg M" first="Mark S." last="Goldberg">Mark S. Goldberg</name><affiliation><nlm:aff id="af75"><addr-line>Department of Medicine</addr-line>,<institution>McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af76"><addr-line>Division of Clinical Epidemiology</addr-line>,<institution>McGill University Health Centre, Royal Victoria Hospital</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Labreche, France" sort="Labreche, France" uniqKey="Labreche F" first="France" last="Labrèche">France Labrèche</name><affiliation><nlm:aff id="af77"><addr-line>Département de Médecine Sociale et Préventive, Département de Santé Environnementale et Santé au travail</addr-line>,<institution>Université de Montréal</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Dumont, Martine" sort="Dumont, Martine" uniqKey="Dumont M" first="Martine" last="Dumont">Martine Dumont</name><affiliation><nlm:aff id="af74"><addr-line>Cancer Genomics Laboratory</addr-line>,<institution>Centre Hospitalier Universitaire de Québec Research Center and Laval University</institution>,<addr-line>Quebec City, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Kristensen, Vessela" sort="Kristensen, Vessela" uniqKey="Kristensen V" first="Vessela" last="Kristensen">Vessela Kristensen</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af79"><addr-line>Institute of Clinical Medicine</addr-line>,<institution>University of Oslo (UiO)</institution>,<addr-line>0450 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Aln S, Grethe Grenaker" sort="Aln S, Grethe Grenaker" uniqKey="Aln S G" first="Grethe Grenaker" last="Aln S">Grethe Grenaker Aln S</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Nord, Silje" sort="Nord, Silje" uniqKey="Nord S" first="Silje" last="Nord">Silje Nord</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Borresen Dale, Anne Lise" sort="Borresen Dale, Anne Lise" uniqKey="Borresen Dale A" first="Anne-Lise" last="Borresen-Dale">Anne-Lise Borresen-Dale</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af79"><addr-line>Institute of Clinical Medicine</addr-line>,<institution>University of Oslo (UiO)</institution>,<addr-line>0450 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Deming Halverson, Sandra" sort="Deming Halverson, Sandra" uniqKey="Deming Halverson S" first="Sandra" last="Deming-Halverson">Sandra Deming-Halverson</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Shrubsole, Martha" sort="Shrubsole, Martha" uniqKey="Shrubsole M" first="Martha" last="Shrubsole">Martha Shrubsole</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Long, Jirong" sort="Long, Jirong" uniqKey="Long J" first="Jirong" last="Long">Jirong Long</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Winqvist, Robert" sort="Winqvist, Robert" uniqKey="Winqvist R" first="Robert" last="Winqvist">Robert Winqvist</name><affiliation><nlm:aff id="af81"><addr-line>Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Pylk S, Katri" sort="Pylk S, Katri" uniqKey="Pylk S K" first="Katri" last="Pylk S">Katri Pylk S</name><affiliation><nlm:aff id="af81"><addr-line>Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Jukkola Vuorinen, Arja" sort="Jukkola Vuorinen, Arja" uniqKey="Jukkola Vuorinen A" first="Arja" last="Jukkola-Vuorinen">Arja Jukkola-Vuorinen</name><affiliation><nlm:aff wicri:cut=" and" id="af82"><addr-line>Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Grip, Mervi" sort="Grip, Mervi" uniqKey="Grip M" first="Mervi" last="Grip">Mervi Grip</name><affiliation><nlm:aff id="af83"><addr-line>Department of Surgery</addr-line>,<institution>Oulu University Hospital, University of Oulu</institution>,<addr-line>Oulu</addr-line>,<country>Finland</country>,</nlm:aff></affiliation></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name><affiliation><nlm:aff wicri:cut=" and" id="af84"><addr-line>Ontario Cancer Genetics Network</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af86"><addr-line>Department of Molecular Genetics</addr-line></nlm:aff></affiliation></author><author><name sortKey="Knight, Julia A" sort="Knight, Julia A" uniqKey="Knight J" first="Julia A." last="Knight">Julia A. Knight</name><affiliation><nlm:aff id="af85"><addr-line>Prosserman Centre for Health Research</addr-line>,<institution>Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af87"><addr-line>Division of Epidemiology, Dalla Lana School of Public Health</addr-line>,<institution>University of Toronto</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name><affiliation><nlm:aff wicri:cut=" and" id="af84"><addr-line>Ontario Cancer Genetics Network</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tchatchou, Sandrine" sort="Tchatchou, Sandrine" uniqKey="Tchatchou S" first="Sandrine" last="Tchatchou">Sandrine Tchatchou</name><affiliation><nlm:aff id="af88"><institution>Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Devilee, Peter" sort="Devilee, Peter" uniqKey="Devilee P" first="Peter" last="Devilee">Peter Devilee</name><affiliation><nlm:aff wicri:cut=" and" id="af89"><addr-line>Department of Human Genetics and Department of Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tollenaar, Robertus A E M" sort="Tollenaar, Robertus A E M" uniqKey="Tollenaar R" first="Robertus A. E. M." last="Tollenaar">Robertus A. E. M. Tollenaar</name><affiliation><nlm:aff id="af90"><addr-line>Department of Surgical Oncology</addr-line>,<institution>Leiden University Medical Center</institution>,<addr-line>2300 RC</addr-line>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Seynaeve, Caroline M" sort="Seynaeve, Caroline M" uniqKey="Seynaeve C" first="Caroline M." last="Seynaeve">Caroline M. Seynaeve</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Van Asperen, Christi J" sort="Van Asperen, Christi J" uniqKey="Van Asperen C" first="Christi J." last="Van Asperen">Christi J. Van Asperen</name><affiliation><nlm:aff id="af92"><addr-line>Department of Clinical Genetics</addr-line>,<institution>Leiden University Medical Center</institution>,<addr-line>P.O. Box 9600, 2300 RC</addr-line>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Garcia Closas, Montserrat" sort="Garcia Closas, Montserrat" uniqKey="Garcia Closas M" first="Montserrat" last="Garcia-Closas">Montserrat Garcia-Closas</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Figueroa, Jonine" sort="Figueroa, Jonine" uniqKey="Figueroa J" first="Jonine" last="Figueroa">Jonine Figueroa</name><affiliation><nlm:aff id="af93"><addr-line>Division of Cancer Epidemiology and Genetics</addr-line>,<institution>National Cancer Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J." last="Chanock">Stephen J. Chanock</name><affiliation><nlm:aff id="af93"><addr-line>Division of Cancer Epidemiology and Genetics</addr-line>,<institution>National Cancer Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Lissowska, Jolanta" sort="Lissowska, Jolanta" uniqKey="Lissowska J" first="Jolanta" last="Lissowska">Jolanta Lissowska</name><affiliation><nlm:aff id="af94"><addr-line>Department of Cancer Epidemiology and Prevention</addr-line>,<institution>M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology</institution>,<addr-line>Warsaw</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Czene, Kamila" sort="Czene, Kamila" uniqKey="Czene K" first="Kamila" last="Czene">Kamila Czene</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Darabi, Hatef" sort="Darabi, Hatef" uniqKey="Darabi H" first="Hatef" last="Darabi">Hatef Darabi</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Mikael" sort="Eriksson, Mikael" uniqKey="Eriksson M" first="Mikael" last="Eriksson">Mikael Eriksson</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Klevebring, Daniel" sort="Klevebring, Daniel" uniqKey="Klevebring D" first="Daniel" last="Klevebring">Daniel Klevebring</name><affiliation><nlm:aff id="af94"><addr-line>Department of Cancer Epidemiology and Prevention</addr-line>,<institution>M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology</institution>,<addr-line>Warsaw</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Hooning, Maartje J" sort="Hooning, Maartje J" uniqKey="Hooning M" first="Maartje J." last="Hooning">Maartje J. Hooning</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Hollestelle, Antoinette" sort="Hollestelle, Antoinette" uniqKey="Hollestelle A" first="Antoinette" last="Hollestelle">Antoinette Hollestelle</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Van Deurzen, Carolien H M" sort="Van Deurzen, Carolien H M" uniqKey="Van Deurzen C" first="Carolien H. M." last="Van Deurzen">Carolien H. M. Van Deurzen</name><affiliation><nlm:aff id="af96"><addr-line>Department of Pathology</addr-line>,<institution>Erasmus University Medical Center</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Kriege, Mieke" sort="Kriege, Mieke" uniqKey="Kriege M" first="Mieke" last="Kriege">Mieke Kriege</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Li, Jingmei" sort="Li, Jingmei" uniqKey="Li J" first="Jingmei" last="Li">Jingmei Li</name><affiliation><nlm:aff id="af97"><addr-line>Human Genetics Division</addr-line>,<institution>Genome Institute of Singapore</institution>,<addr-line>Singapore 138672</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="af97"><addr-line>Human Genetics Division</addr-line>,<institution>Genome Institute of Singapore</institution>,<addr-line>Singapore 138672</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Humphreys, Keith" sort="Humphreys, Keith" uniqKey="Humphreys K" first="Keith" last="Humphreys">Keith Humphreys</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Cox, Angela" sort="Cox, Angela" uniqKey="Cox A" first="Angela" last="Cox">Angela Cox</name><affiliation><nlm:aff id="af98"><addr-line>Sheffield Cancer Research, Department of Oncology</addr-line>,<institution>University of Sheffield</institution>,<addr-line>Sheffield</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Cross, Simon S" sort="Cross, Simon S" uniqKey="Cross S" first="Simon S." last="Cross">Simon S. Cross</name><affiliation><nlm:aff id="af99"><addr-line>Academic Unit of Pathology, Department of Neuroscience</addr-line>,<institution>University of Sheffield</institution>,<addr-line>Sheffield</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Reed, Malcolm W R" sort="Reed, Malcolm W R" uniqKey="Reed M" first="Malcolm W. R." last="Reed">Malcolm W. R. Reed</name><affiliation><nlm:aff id="af100"><addr-line>Brighton and Sussex Medical School</addr-line>,<institution>University of Sussex</institution>,<addr-line>Brighton, East Sussex</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Pharoah, Paul D P" sort="Pharoah, Paul D P" uniqKey="Pharoah P" first="Paul D. P." last="Pharoah">Paul D. P. Pharoah</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dunning, Alison M" sort="Dunning, Alison M" uniqKey="Dunning A" first="Alison M." last="Dunning">Alison M. Dunning</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shah, Mitul" sort="Shah, Mitul" uniqKey="Shah M" first="Mitul" last="Shah">Mitul Shah</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Perkins, Barbara J" sort="Perkins, Barbara J" uniqKey="Perkins B" first="Barbara J." last="Perkins">Barbara J. Perkins</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Jakubowska, Anna" sort="Jakubowska, Anna" uniqKey="Jakubowska A" first="Anna" last="Jakubowska">Anna Jakubowska</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Lubinski, Jan" sort="Lubinski, Jan" uniqKey="Lubinski J" first="Jan" last="Lubinski">Jan Lubinski</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Jaworska Bieniek, Katarzyna" sort="Jaworska Bieniek, Katarzyna" uniqKey="Jaworska Bieniek K" first="Katarzyna" last="Jaworska-Bieniek">Katarzyna Jaworska-Bieniek</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Durda, Katarzyna" sort="Durda, Katarzyna" uniqKey="Durda K" first="Katarzyna" last="Durda">Katarzyna Durda</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Ashworth, Alan" sort="Ashworth, Alan" uniqKey="Ashworth A" first="Alan" last="Ashworth">Alan Ashworth</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Swerdlow, Anthony" sort="Swerdlow, Anthony" uniqKey="Swerdlow A" first="Anthony" last="Swerdlow">Anthony Swerdlow</name><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Jones, Michael" sort="Jones, Michael" uniqKey="Jones M" first="Michael" last="Jones">Michael Jones</name><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Schoemaker, Minouk J" sort="Schoemaker, Minouk J" uniqKey="Schoemaker M" first="Minouk J." last="Schoemaker">Minouk J. Schoemaker</name><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Meindl, Alfons" sort="Meindl, Alfons" uniqKey="Meindl A" first="Alfons" last="Meindl">Alfons Meindl</name><affiliation><nlm:aff id="af102"><addr-line>Division of Gynaecology and Obstetrics</addr-line>,<institution>Technische Universität München</institution>,<addr-line>81675 Munich</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Schmutzler, Rita K" sort="Schmutzler, Rita K" uniqKey="Schmutzler R" first="Rita K." last="Schmutzler">Rita K. Schmutzler</name><affiliation><nlm:aff id="af103"><addr-line>Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), Medical Faculty</addr-line>,<institution>University of Cologne and University Hospital Cologne</institution>,<addr-line>Cologne</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Olswold, Curtis" sort="Olswold, Curtis" uniqKey="Olswold C" first="Curtis" last="Olswold">Curtis Olswold</name><affiliation><nlm:aff wicri:cut=" and" id="af68"><addr-line>Department of Laboratory Medicine and Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Slager, Susan" sort="Slager, Susan" uniqKey="Slager S" first="Susan" last="Slager">Susan Slager</name><affiliation><nlm:aff wicri:cut=" and" id="af68"><addr-line>Department of Laboratory Medicine and Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Toland, Amanda E" sort="Toland, Amanda E" uniqKey="Toland A" first="Amanda E." last="Toland">Amanda E. Toland</name><affiliation><nlm:aff id="af104"><addr-line>Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center</addr-line>,<institution>The Ohio State University</institution>,<addr-line>Columbus, OH</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Yannoukakos, Drakoulis" sort="Yannoukakos, Drakoulis" uniqKey="Yannoukakos D" first="Drakoulis" last="Yannoukakos">Drakoulis Yannoukakos</name><affiliation><nlm:aff id="af105"><addr-line>Molecular Diagnostics Laboratory</addr-line>,<institution>IRRP, National Centre for Scientific Research ‘Demokritos’, Aghia Paraskevi Attikis</institution>,<addr-line>Athens</addr-line>,<country>Greece</country>,</nlm:aff></affiliation></author><author><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation><nlm:aff id="af106"><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af107"><addr-line>Institute of Population Health</addr-line>,<institution>University of Manchester</institution>,<addr-line>Manchester</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Lophatananon, Artitaya" sort="Lophatananon, Artitaya" uniqKey="Lophatananon A" first="Artitaya" last="Lophatananon">Artitaya Lophatananon</name><affiliation><nlm:aff id="af106"><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Stewart Brown, Sarah" sort="Stewart Brown, Sarah" uniqKey="Stewart Brown S" first="Sarah" last="Stewart-Brown">Sarah Stewart-Brown</name><affiliation><nlm:aff id="af106"><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Siriwanarangsan, Pornthep" sort="Siriwanarangsan, Pornthep" uniqKey="Siriwanarangsan P" first="Pornthep" last="Siriwanarangsan">Pornthep Siriwanarangsan</name><affiliation><nlm:aff id="af108"><institution>Ministry of Public Health</institution>,<addr-line>Nonthaburi</addr-line>,<country>Thailand</country>,</nlm:aff></affiliation></author><author><name sortKey="Matsuo, Keitaro" sort="Matsuo, Keitaro" uniqKey="Matsuo K" first="Keitaro" last="Matsuo">Keitaro Matsuo</name><affiliation><nlm:aff id="af109"><addr-line>Department of Preventive Medicine</addr-line>,<institution>Kyushu University Faculty of Medical Sciences</institution>,<addr-line>Fukuoka</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Ito, Hidema" sort="Ito, Hidema" uniqKey="Ito H" first="Hidema" last="Ito">Hidema Ito</name><affiliation><nlm:aff id="af110"><addr-line>Division of Epidemiology and Prevention</addr-line>,<institution>Aichi Cancer Center Research Institute</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Iwata, Hiroji" sort="Iwata, Hiroji" uniqKey="Iwata H" first="Hiroji" last="Iwata">Hiroji Iwata</name><affiliation><nlm:aff id="af111"><addr-line>Department of Breast Oncology</addr-line>,<institution>Aichi Cancer Center Hospital</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Ishiguro, Junko" sort="Ishiguro, Junko" uniqKey="Ishiguro J" first="Junko" last="Ishiguro">Junko Ishiguro</name><affiliation><nlm:aff id="af111"><addr-line>Department of Breast Oncology</addr-line>,<institution>Aichi Cancer Center Hospital</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H." last="Wu">Anna H. Wu</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Tseng, Chiu Chen" sort="Tseng, Chiu Chen" uniqKey="Tseng C" first="Chiu-Chen" last="Tseng">Chiu-Chen Tseng</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Van Den Berg, David" sort="Van Den Berg, David" uniqKey="Van Den Berg D" first="David" last="Van Den Berg">David Van Den Berg</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Stram, Daniel O" sort="Stram, Daniel O" uniqKey="Stram D" first="Daniel O." last="Stram">Daniel O. Stram</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Teo, Soo Hwang" sort="Teo, Soo Hwang" uniqKey="Teo S" first="Soo Hwang" last="Teo">Soo Hwang Teo</name><affiliation><nlm:aff id="af112"><addr-line>Cancer Research Initiatives Foundation</addr-line>,<institution>Sime Darby Medical Centre</institution>,<addr-line>Subang Jaya, Selangor</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af113"><addr-line>Breast Cancer Research Unit, University Malaya Cancer Research Institute</addr-line>,<institution>University Malaya Medical Centre</institution>,<addr-line>Kuala Lumpur</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation></author><author><name sortKey="Yip, Cheng Har" sort="Yip, Cheng Har" uniqKey="Yip C" first="Cheng Har" last="Yip">Cheng Har Yip</name><affiliation><nlm:aff id="af113"><addr-line>Breast Cancer Research Unit, University Malaya Cancer Research Institute</addr-line>,<institution>University Malaya Medical Centre</institution>,<addr-line>Kuala Lumpur</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation></author><author><name sortKey="Kang, Peter" sort="Kang, Peter" uniqKey="Kang P" first="Peter" last="Kang">Peter Kang</name><affiliation><nlm:aff id="af112"><addr-line>Cancer Research Initiatives Foundation</addr-line>,<institution>Sime Darby Medical Centre</institution>,<addr-line>Subang Jaya, Selangor</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation></author><author><name sortKey="Ikram, Mohammad Kamran" sort="Ikram, Mohammad Kamran" uniqKey="Ikram M" first="Mohammad Kamran" last="Ikram">Mohammad Kamran Ikram</name><affiliation><nlm:aff id="af114"><addr-line>Singapore Eye Research Institute</addr-line>,<institution>National University of Singapore</institution>,<addr-line>168751 Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Shu, Xiao Ou" sort="Shu, Xiao Ou" uniqKey="Shu X" first="Xiao-Ou" last="Shu">Xiao-Ou Shu</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name><affiliation><nlm:aff id="af115"><institution>Shanghai Center for Disease Control and Prevention</institution>,<addr-line>Shanghai</addr-line>,<country>China</country>,</nlm:aff></affiliation></author><author><name sortKey="Gao, Yu Tang" sort="Gao, Yu Tang" uniqKey="Gao Y" first="Yu-Tang" last="Gao">Yu-Tang Gao</name><affiliation><nlm:aff id="af116"><addr-line>Department of Epidemiology</addr-line>,<institution>Shanghai Cancer Institute</institution>,<addr-line>Shanghai</addr-line>,<country>China</country>,</nlm:aff></affiliation></author><author><name sortKey="Cai, Hui" sort="Cai, Hui" uniqKey="Cai H" first="Hui" last="Cai">Hui Cai</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Kang, Daehee" sort="Kang, Daehee" uniqKey="Kang D" first="Daehee" last="Kang">Daehee Kang</name><affiliation><nlm:aff wicri:cut=" and" id="af117"><addr-line>Department of Preventive Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af119"><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af120"><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Choi, Ji Yeob" sort="Choi, Ji Yeob" uniqKey="Choi J" first="Ji-Yeob" last="Choi">Ji-Yeob Choi</name><affiliation><nlm:aff id="af119"><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af120"><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Park, Sue K" sort="Park, Sue K" uniqKey="Park S" first="Sue K." last="Park">Sue K. Park</name><affiliation><nlm:aff wicri:cut=" and" id="af117"><addr-line>Department of Preventive Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af119"><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af120"><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Noh, Dong Young" sort="Noh, Dong Young" uniqKey="Noh D" first="Dong-Young" last="Noh">Dong-Young Noh</name><affiliation><nlm:aff id="af118"><addr-line>Department of Surgery</addr-line>,<institution>Seoul National University College of Medicine</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Hartman, Mikael" sort="Hartman, Mikael" uniqKey="Hartman M" first="Mikael" last="Hartman">Mikael Hartman</name><affiliation><nlm:aff wicri:cut=" and" id="af121"><addr-line>Saw Swee Hock School of Public Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af122"><addr-line>Department of Surgery, Yong Loo Lin School of Medicine</addr-line>,<institution>National University of Singapore</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af123"><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Miao, Hui" sort="Miao, Hui" uniqKey="Miao H" first="Hui" last="Miao">Hui Miao</name><affiliation><nlm:aff wicri:cut=" and" id="af121"><addr-line>Saw Swee Hock School of Public Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af123"><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Lim, Wei Yen" sort="Lim, Wei Yen" uniqKey="Lim W" first="Wei Yen" last="Lim">Wei Yen Lim</name><affiliation><nlm:aff wicri:cut=" and" id="af121"><addr-line>Saw Swee Hock School of Public Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af123"><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Lee, Soo Chin" sort="Lee, Soo Chin" uniqKey="Lee S" first="Soo Chin" last="Lee">Soo Chin Lee</name><affiliation><nlm:aff id="af124"><addr-line>Department of Haematology-Oncology</addr-line>,<institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af125"><addr-line>Cancer Science Institute of Singapore</addr-line>,<institution>National University Singapore</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Sangrajrang, Suleeporn" sort="Sangrajrang, Suleeporn" uniqKey="Sangrajrang S" first="Suleeporn" last="Sangrajrang">Suleeporn Sangrajrang</name><affiliation><nlm:aff id="af126"><institution>National Cancer Institute</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country>,</nlm:aff></affiliation></author><author><name sortKey="Gaborieau, Valerie" sort="Gaborieau, Valerie" uniqKey="Gaborieau V" first="Valerie" last="Gaborieau">Valerie Gaborieau</name><affiliation><nlm:aff id="af127"><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Brennan, Paul" sort="Brennan, Paul" uniqKey="Brennan P" first="Paul" last="Brennan">Paul Brennan</name><affiliation><nlm:aff id="af127"><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Mckay, James" sort="Mckay, James" uniqKey="Mckay J" first="James" last="Mckay">James Mckay</name><affiliation><nlm:aff id="af127"><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Wu, Pei Ei" sort="Wu, Pei Ei" uniqKey="Wu P" first="Pei-Ei" last="Wu">Pei-Ei Wu</name><affiliation><nlm:aff wicri:cut=" and" id="af128"><addr-line>Taiwan Biobank</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af129"><addr-line>Institute of Biomedical Sciences</addr-line>,<institution>Academia Sinica</institution>,<addr-line>Taipei 115</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Hou, Ming Feng" sort="Hou, Ming Feng" uniqKey="Hou M" first="Ming-Feng" last="Hou">Ming-Feng Hou</name><affiliation><nlm:aff id="af130"><addr-line>Cancer Center and Department of Surgery</addr-line>,<institution>Kaohsiung Medical University Chung-Ho Memorial Hospital</institution>,<addr-line>Kaohsiung 804</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Yu, Jyh Cherng" sort="Yu, Jyh Cherng" uniqKey="Yu J" first="Jyh-Cherng" last="Yu">Jyh-Cherng Yu</name><affiliation><nlm:aff id="af131"><addr-line>Department of Surgery</addr-line>,<institution>Tri-Service General Hospital and National Defense Medical Center</institution>,<addr-line>Taipei 114</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Shen, Chen Yang" sort="Shen, Chen Yang" uniqKey="Shen C" first="Chen-Yang" last="Shen">Chen-Yang Shen</name><affiliation><nlm:aff id="af130"><addr-line>Cancer Center and Department of Surgery</addr-line>,<institution>Kaohsiung Medical University Chung-Ho Memorial Hospital</institution>,<addr-line>Kaohsiung 804</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af132"><addr-line>School of Public Health</addr-line>,<institution>China Medical University</institution>,<addr-line>Taichung 404</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Blot, William" sort="Blot, William" uniqKey="Blot W" first="William" last="Blot">William Blot</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af133"><institution>International Epidemiology Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Cai, Qiuyin" sort="Cai, Qiuyin" uniqKey="Cai Q" first="Qiuyin" last="Cai">Qiuyin Cai</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Signorello, Lisa B" sort="Signorello, Lisa B" uniqKey="Signorello L" first="Lisa B." last="Signorello">Lisa B. Signorello</name><affiliation><nlm:aff id="af134"><institution>Dana-Farber/Harvard Cancer Center</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af135"><addr-line>Department of Epidemiology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Luccarini, Craig" sort="Luccarini, Craig" uniqKey="Luccarini C" first="Craig" last="Luccarini">Craig Luccarini</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bayes, Caroline" sort="Bayes, Caroline" uniqKey="Bayes C" first="Caroline" last="Bayes">Caroline Bayes</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ahmed, Shahana" sort="Ahmed, Shahana" uniqKey="Ahmed S" first="Shahana" last="Ahmed">Shahana Ahmed</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Maranian, Mel" sort="Maranian, Mel" uniqKey="Maranian M" first="Mel" last="Maranian">Mel Maranian</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Healey, Catherine S" sort="Healey, Catherine S" uniqKey="Healey C" first="Catherine S." last="Healey">Catherine S. Healey</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gonzalez Neira, Anna" sort="Gonzalez Neira, Anna" uniqKey="Gonzalez Neira A" first="Anna" last="González-Neira">Anna González-Neira</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Pita, Guillermo" sort="Pita, Guillermo" uniqKey="Pita G" first="Guillermo" last="Pita">Guillermo Pita</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Alonso, M Rosario" sort="Alonso, M Rosario" uniqKey="Alonso M" first="M. Rosario" last="Alonso">M. Rosario Alonso</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Alvarez, Nuria" sort="Alvarez, Nuria" uniqKey="Alvarez N" first="Nuria" last="Álvarez">Nuria Álvarez</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Herrero, Daniel" sort="Herrero, Daniel" uniqKey="Herrero D" first="Daniel" last="Herrero">Daniel Herrero</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Tessier, Daniel C" sort="Tessier, Daniel C" uniqKey="Tessier D" first="Daniel C." last="Tessier">Daniel C. Tessier</name><affiliation><nlm:aff id="af138"><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Vincent, Daniel" sort="Vincent, Daniel" uniqKey="Vincent D" first="Daniel" last="Vincent">Daniel Vincent</name><affiliation><nlm:aff id="af138"><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Bacot, Francois" sort="Bacot, Francois" uniqKey="Bacot F" first="Francois" last="Bacot">Francois Bacot</name><affiliation><nlm:aff id="af138"><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="af136"><addr-line>Program in Molecular and Genetic Epidemiology</addr-line>,<institution>Harvard School of Public Health</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindstrom">Sara Lindstrom</name><affiliation><nlm:aff id="af136"><addr-line>Program in Molecular and Genetic Epidemiology</addr-line>,<institution>Harvard School of Public Health</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Dennis, Joe" sort="Dennis, Joe" uniqKey="Dennis J" first="Joe" last="Dennis">Joe Dennis</name><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Michailidou, Kyriaki" sort="Michailidou, Kyriaki" uniqKey="Michailidou K" first="Kyriaki" last="Michailidou">Kyriaki Michailidou</name><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Bolla, Manjeet K" sort="Bolla, Manjeet K" uniqKey="Bolla M" first="Manjeet K." last="Bolla">Manjeet K. Bolla</name><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F." last="Easton">Douglas F. Easton</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Dos Santos Silva, Isabel" sort="Dos Santos Silva, Isabel" uniqKey="Dos Santos Silva I" first="Isabel" last="Dos Santos Silva">Isabel Dos Santos Silva</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Fletcher, Olivia" sort="Fletcher, Olivia" uniqKey="Fletcher O" first="Olivia" last="Fletcher">Olivia Fletcher</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Peto, Julian" sort="Peto, Julian" uniqKey="Peto J" first="Julian" last="Peto">Julian Peto</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25652398</idno><idno type="pmc">4406292</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406292</idno><idno type="RBID">PMC:4406292</idno><idno type="doi">10.1093/hmg/ddv035</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">002579</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002579</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2</title><author><name sortKey="Orr, Nick" sort="Orr, Nick" uniqKey="Orr N" first="Nick" last="Orr">Nick Orr</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dudbridge, Frank" sort="Dudbridge, Frank" uniqKey="Dudbridge F" first="Frank" last="Dudbridge">Frank Dudbridge</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Dryden, Nicola" sort="Dryden, Nicola" uniqKey="Dryden N" first="Nicola" last="Dryden">Nicola Dryden</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Maguire, Sarah" sort="Maguire, Sarah" uniqKey="Maguire S" first="Sarah" last="Maguire">Sarah Maguire</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Novo, Daniela" sort="Novo, Daniela" uniqKey="Novo D" first="Daniela" last="Novo">Daniela Novo</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Perrakis, Eleni" sort="Perrakis, Eleni" uniqKey="Perrakis E" first="Eleni" last="Perrakis">Eleni Perrakis</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Johnson, Nichola" sort="Johnson, Nichola" uniqKey="Johnson N" first="Nichola" last="Johnson">Nichola Johnson</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ghoussaini, Maya" sort="Ghoussaini, Maya" uniqKey="Ghoussaini M" first="Maya" last="Ghoussaini">Maya Ghoussaini</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation><nlm:aff id="af8"><addr-line>Department of Pathology</addr-line>,<institution>The University of Melbourne</institution>,<addr-line>Melbourne, VIC 3010</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Apicella, Carmel" sort="Apicella, Carmel" uniqKey="Apicella C" first="Carmel" last="Apicella">Carmel Apicella</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation></author><author><name sortKey="Stone, Jennifer" sort="Stone, Jennifer" uniqKey="Stone J" first="Jennifer" last="Stone">Jennifer Stone</name><affiliation><nlm:aff id="af9"><addr-line>Centre for Genetic Origins of Health and Disease</addr-line>,<institution>University of Western Australia</institution>,<addr-line>Perth, WA</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Marjanka K" sort="Schmidt, Marjanka K" uniqKey="Schmidt M" first="Marjanka K." last="Schmidt">Marjanka K. Schmidt</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Broeks, Annegien" sort="Broeks, Annegien" uniqKey="Broeks A" first="Annegien" last="Broeks">Annegien Broeks</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Van T Veer, Laura J" sort="Van T Veer, Laura J" uniqKey="Van T Veer L" first="Laura J." last="Van'T Veer">Laura J. Van'T Veer</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Hogervorst, Frans B" sort="Hogervorst, Frans B" uniqKey="Hogervorst F" first="Frans B." last="Hogervorst">Frans B. Hogervorst</name><affiliation><nlm:aff id="af10"><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Fasching, Peter A" sort="Fasching, Peter A" uniqKey="Fasching P" first="Peter A." last="Fasching">Peter A. Fasching</name><affiliation><nlm:aff wicri:cut=" and" id="af11"><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af13"><addr-line>David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology</addr-line>,<institution>University of California at Los Angeles</institution>,<addr-line>Los Angeles, CA 90095</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Haeberle, Lothar" sort="Haeberle, Lothar" uniqKey="Haeberle L" first="Lothar" last="Haeberle">Lothar Haeberle</name><affiliation><nlm:aff wicri:cut=" and" id="af11"><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ekici, Arif B" sort="Ekici, Arif B" uniqKey="Ekici A" first="Arif B." last="Ekici">Arif B. Ekici</name><affiliation><nlm:aff id="af12"><addr-line>Institute of Human Genetics, University Hospital Erlangen</addr-line>,<institution>Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN</institution>,<addr-line>91054 Erlangen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Beckmann, Matthias W" sort="Beckmann, Matthias W" uniqKey="Beckmann M" first="Matthias W." last="Beckmann">Matthias W. Beckmann</name><affiliation><nlm:aff wicri:cut=" and" id="af11"><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gibson, Lorna" sort="Gibson, Lorna" uniqKey="Gibson L" first="Lorna" last="Gibson">Lorna Gibson</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Aitken, Zoe" sort="Aitken, Zoe" uniqKey="Aitken Z" first="Zoe" last="Aitken">Zoe Aitken</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Warren, Helen" sort="Warren, Helen" uniqKey="Warren H" first="Helen" last="Warren">Helen Warren</name><affiliation><nlm:aff wicri:cut=" and" id="af14"><addr-line>Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af15"><addr-line>NIHR Barts Cardiovascular Biomedical Research Unit</addr-line>,<institution>Queen Mary University of London</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Sawyer, Elinor" sort="Sawyer, Elinor" uniqKey="Sawyer E" first="Elinor" last="Sawyer">Elinor Sawyer</name><affiliation><nlm:aff id="af16"><addr-line>Division of Cancer Studies</addr-line>,<institution>Kings College London, Guy's Hospital</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Tomlinson, Ian" sort="Tomlinson, Ian" uniqKey="Tomlinson I" first="Ian" last="Tomlinson">Ian Tomlinson</name><affiliation><nlm:aff id="af17"><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre</addr-line>,<institution>University of Oxford</institution>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Kerin, Michael J" sort="Kerin, Michael J" uniqKey="Kerin M" first="Michael J." last="Kerin">Michael J. Kerin</name><affiliation><nlm:aff id="af18"><addr-line>Clinical Science Institute</addr-line>,<institution>University Hospital Galway</institution>,<addr-line>Galway</addr-line>,<country>Ireland</country>,</nlm:aff></affiliation></author><author><name sortKey="Miller, Nicola" sort="Miller, Nicola" uniqKey="Miller N" first="Nicola" last="Miller">Nicola Miller</name><affiliation><nlm:aff id="af18"><addr-line>Clinical Science Institute</addr-line>,<institution>University Hospital Galway</institution>,<addr-line>Galway</addr-line>,<country>Ireland</country>,</nlm:aff></affiliation></author><author><name sortKey="Burwinkel, Barbara" sort="Burwinkel, Barbara" uniqKey="Burwinkel B" first="Barbara" last="Burwinkel">Barbara Burwinkel</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af21"><addr-line>Molecular Epidemiology Group</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Marme, Frederik" sort="Marme, Frederik" uniqKey="Marme F" first="Frederik" last="Marme">Frederik Marme</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af20"><addr-line>National Center for Tumor Diseases</addr-line>,<institution>University of Heidelberg</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Schneeweiss, Andreas" sort="Schneeweiss, Andreas" uniqKey="Schneeweiss A" first="Andreas" last="Schneeweiss">Andreas Schneeweiss</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af20"><addr-line>National Center for Tumor Diseases</addr-line>,<institution>University of Heidelberg</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Sohn, Chistof" sort="Sohn, Chistof" uniqKey="Sohn C" first="Chistof" last="Sohn">Chistof Sohn</name><affiliation><nlm:aff wicri:cut=" and" id="af19"><addr-line>Department of Obstetrics and Gynecology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Guenel, Pascal" sort="Guenel, Pascal" uniqKey="Guenel P" first="Pascal" last="Guénel">Pascal Guénel</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Truong, Therese" sort="Truong, Therese" uniqKey="Truong T" first="Thérèse" last="Truong">Thérèse Truong</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Cordina Duverger, Emilie" sort="Cordina Duverger, Emilie" uniqKey="Cordina Duverger E" first="Emilie" last="Cordina-Duverger">Emilie Cordina-Duverger</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Sanchez, Marie" sort="Sanchez, Marie" uniqKey="Sanchez M" first="Marie" last="Sanchez">Marie Sanchez</name><affiliation><nlm:aff id="af22"><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af23"><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Bojesen, Stig E" sort="Bojesen, Stig E" uniqKey="Bojesen S" first="Stig E." last="Bojesen">Stig E. Bojesen</name><affiliation><nlm:aff wicri:cut=" and" id="af24"><addr-line>Copenhagen General Population Study</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af25"><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Nordestgaard, B Rge G" sort="Nordestgaard, B Rge G" uniqKey="Nordestgaard B" first="B Rge G." last="Nordestgaard">B Rge G. Nordestgaard</name><affiliation><nlm:aff wicri:cut=" and" id="af24"><addr-line>Copenhagen General Population Study</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af25"><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Nielsen, Sune F" sort="Nielsen, Sune F" uniqKey="Nielsen S" first="Sune F." last="Nielsen">Sune F. Nielsen</name><affiliation><nlm:aff wicri:cut=" and" id="af24"><addr-line>Copenhagen General Population Study</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af25"><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Flyger, Henrik" sort="Flyger, Henrik" uniqKey="Flyger H" first="Henrik" last="Flyger">Henrik Flyger</name><affiliation><nlm:aff id="af26"><addr-line>Department of Breast Surgery</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>Copenhagen</addr-line>,<country>Denmark</country>,</nlm:aff></affiliation></author><author><name sortKey="Benitez, Javier" sort="Benitez, Javier" uniqKey="Benitez J" first="Javier" last="Benitez">Javier Benitez</name><affiliation><nlm:aff id="af27"><addr-line>Human Genetics Group, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>28029 Madrid</addr-line>,<country>Spain</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af28"><institution>Centro de Investigación en Red de Enfermedades Raras (CIBERER)</institution>,<addr-line>46010 Valencia</addr-line>,<country>Spain</country>,</nlm:aff></affiliation></author><author><name sortKey="Zamora, Maria Pilar" sort="Zamora, Maria Pilar" uniqKey="Zamora M" first="Maria Pilar" last="Zamora">Maria Pilar Zamora</name><affiliation><nlm:aff id="af29"><addr-line>Servicio de Oncología Médica</addr-line>,<institution>Hospital Universitario La Paz</institution>,<addr-line>28046 Madrid</addr-line>,<country>Spain</country>,</nlm:aff></affiliation></author><author><name sortKey="Arias Perez, Jose Ignacio" sort="Arias Perez, Jose Ignacio" uniqKey="Arias Perez J" first="Jose Ignacio" last="Arias Perez">Jose Ignacio Arias Perez</name><affiliation><nlm:aff wicri:cut=" and" id="af30"><addr-line>Servicio de Cirugía General y Especialidades</addr-line></nlm:aff></affiliation></author><author><name sortKey="Menendez, Primitiva" sort="Menendez, Primitiva" uniqKey="Menendez P" first="Primitiva" last="Menéndez">Primitiva Menéndez</name><affiliation><nlm:aff id="af31"><addr-line>Servicio de Anatomía Patológica</addr-line>,<institution>Hospital Monte Naranco</institution>,<addr-line>33012 Oviedo</addr-line>,<country>Spain</country>,</nlm:aff></affiliation></author><author><name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name><affiliation><nlm:aff id="af32"><addr-line>Department of Epidemiology</addr-line>,<institution>University of California Irvine</institution>,<addr-line>Irvine, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Neuhausen, Susan L" sort="Neuhausen, Susan L" uniqKey="Neuhausen S" first="Susan L." last="Neuhausen">Susan L. Neuhausen</name><affiliation><nlm:aff id="af33"><institution>Beckman Research Institute of City of Hope</institution>,<addr-line>Duarte, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation><nlm:aff id="af34"><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Dieffenbach, Aida Karina" sort="Dieffenbach, Aida Karina" uniqKey="Dieffenbach A" first="Aida Karina" last="Dieffenbach">Aida Karina Dieffenbach</name><affiliation><nlm:aff id="af34"><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Arndt, Volker" sort="Arndt, Volker" uniqKey="Arndt V" first="Volker" last="Arndt">Volker Arndt</name><affiliation><nlm:aff id="af34"><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Stegmaier, Christa" sort="Stegmaier, Christa" uniqKey="Stegmaier C" first="Christa" last="Stegmaier">Christa Stegmaier</name><affiliation><nlm:aff id="af38"><institution>Saarland Cancer Registry</institution>,<addr-line>Saarbrücken</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Hamann, Ute" sort="Hamann, Ute" uniqKey="Hamann U" first="Ute" last="Hamann">Ute Hamann</name><affiliation><nlm:aff wicri:cut=" and" id="af36"><addr-line>Molecular Genetics of Breast Cancer</addr-line></nlm:aff></affiliation></author><author><name sortKey="Brauch, Hiltrud" sort="Brauch, Hiltrud" uniqKey="Brauch H" first="Hiltrud" last="Brauch">Hiltrud Brauch</name><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff id="af39"><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af40"><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Justenhoven, Christina" sort="Justenhoven, Christina" uniqKey="Justenhoven C" first="Christina" last="Justenhoven">Christina Justenhoven</name><affiliation><nlm:aff id="af39"><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af40"><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Bruning, Thomas" sort="Bruning, Thomas" uniqKey="Bruning T" first="Thomas" last="Brüning">Thomas Brüning</name><affiliation><nlm:aff id="af41"><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr—University Bochum (IPA)</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Ko, Yon Dschun" sort="Ko, Yon Dschun" uniqKey="Ko Y" first="Yon-Dschun" last="Ko">Yon-Dschun Ko</name><affiliation><nlm:aff id="af42"><addr-line>Department of Internal Medicine</addr-line>,<institution>Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af35"><addr-line>German Cancer Consortium (DKTK)</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af36"><addr-line>Molecular Genetics of Breast Cancer</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af39"><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af40"><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af41"><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr—University Bochum (IPA)</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af42"><addr-line>Department of Internal Medicine</addr-line>,<institution>Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af43"><addr-line>Institute of Pathology</addr-line>,<institution>Medical Faculty of the University of Bonn</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af44"><addr-line>Institute of Occupational Medicine and Maritime Medicine</addr-line>,<institution>University Medical Center Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name><affiliation><nlm:aff id="af45"><addr-line>Department of Obstetrics and Gynecology</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Aittom Ki, Kristiina" sort="Aittom Ki, Kristiina" uniqKey="Aittom Ki K" first="Kristiina" last="Aittom Ki">Kristiina Aittom Ki</name><affiliation><nlm:aff wicri:cut=" and" id="af46"><addr-line>Department of Clinical Genetics</addr-line></nlm:aff></affiliation></author><author><name sortKey="Blomqvist, Carl" sort="Blomqvist, Carl" uniqKey="Blomqvist C" first="Carl" last="Blomqvist">Carl Blomqvist</name><affiliation><nlm:aff id="af47"><addr-line>Department of Oncology</addr-line>,<institution>University of Helsinki and Helsinki University Hospital</institution>,<addr-line>Helsinki</addr-line>,<country>Finland</country>,</nlm:aff></affiliation></author><author><name sortKey="Khan, Sofia" sort="Khan, Sofia" uniqKey="Khan S" first="Sofia" last="Khan">Sofia Khan</name><affiliation><nlm:aff id="af45"><addr-line>Department of Obstetrics and Gynecology</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Bogdanova, Natalia" sort="Bogdanova, Natalia" uniqKey="Bogdanova N" first="Natalia" last="Bogdanova">Natalia Bogdanova</name><affiliation><nlm:aff wicri:cut=" and" id="af48"><addr-line>Department of Radiation Oncology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af49"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Hannover Medical School</institution>,<addr-line>Hannover</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Dork, Thilo" sort="Dork, Thilo" uniqKey="Dork T" first="Thilo" last="Dörk">Thilo Dörk</name><affiliation><nlm:aff id="af49"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Hannover Medical School</institution>,<addr-line>Hannover</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Lindblom, Annika" sort="Lindblom, Annika" uniqKey="Lindblom A" first="Annika" last="Lindblom">Annika Lindblom</name><affiliation><nlm:aff wicri:cut=" and" id="af50"><addr-line>Department of Molecular Medicine and Surgery</addr-line></nlm:aff></affiliation></author><author><name sortKey="Margolin, Sara" sort="Margolin, Sara" uniqKey="Margolin S" first="Sara" last="Margolin">Sara Margolin</name><affiliation><nlm:aff id="af51"><addr-line>Department of Oncology-Pathology</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Mannermaa, Arto" sort="Mannermaa, Arto" uniqKey="Mannermaa A" first="Arto" last="Mannermaa">Arto Mannermaa</name><affiliation><nlm:aff wicri:cut=" and" id="af52"><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af54"><addr-line>Imaging Center, Department of Clinical Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kataja, Vesa" sort="Kataja, Vesa" uniqKey="Kataja V" first="Vesa" last="Kataja">Vesa Kataja</name><affiliation><nlm:aff id="af53"><addr-line>School of Medicine, Institute of Clinical Medicine, Oncology</addr-line>,<institution>University of Eastern Finland</institution>,<addr-line>Kuopio</addr-line>,<country>Finland</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af55"><addr-line>Biocenter Kuopio, Cancer Center of Eastern Finland</addr-line>,<institution>Kuopio University Hospital</institution>,<addr-line>Kuopio</addr-line>,<country>Finland</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af56"><addr-line>Central Finland Health Care District</addr-line>,<institution>Jyväskylä Central Hospital</institution>,<addr-line>Jyväskylä</addr-line>,<country>Finland</country>,</nlm:aff></affiliation></author><author><name sortKey="Kosma, Veli Matti" sort="Kosma, Veli Matti" uniqKey="Kosma V" first="Veli-Matti" last="Kosma">Veli-Matti Kosma</name><affiliation><nlm:aff wicri:cut=" and" id="af52"><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af54"><addr-line>Imaging Center, Department of Clinical Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hartikainen, Jaana M" sort="Hartikainen, Jaana M" uniqKey="Hartikainen J" first="Jaana M." last="Hartikainen">Jaana M. Hartikainen</name><affiliation><nlm:aff wicri:cut=" and" id="af52"><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af54"><addr-line>Imaging Center, Department of Clinical Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name><affiliation><nlm:aff id="af57"><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name><affiliation><nlm:aff id="af57"><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af58"><institution>Peter MacCallum Cancer Center</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af57"><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af58"><institution>Peter MacCallum Cancer Center</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Lambrechts, Diether" sort="Lambrechts, Diether" uniqKey="Lambrechts D" first="Diether" last="Lambrechts">Diether Lambrechts</name><affiliation><nlm:aff id="af59"><addr-line>Vesalius Research Center (VRC)</addr-line>,<institution>VIB</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af60"><addr-line>Laboratory for Translational Genetics, Department of Oncology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Moisse, Matthieu" sort="Moisse, Matthieu" uniqKey="Moisse M" first="Matthieu" last="Moisse">Matthieu Moisse</name><affiliation><nlm:aff id="af59"><addr-line>Vesalius Research Center (VRC)</addr-line>,<institution>VIB</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af60"><addr-line>Laboratory for Translational Genetics, Department of Oncology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Floris, Guiseppe" sort="Floris, Guiseppe" uniqKey="Floris G" first="Guiseppe" last="Floris">Guiseppe Floris</name><affiliation><nlm:aff id="af61"><institution>University Hospital Gasthuisberg</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Beuselinck, Benoit" sort="Beuselinck, Benoit" uniqKey="Beuselinck B" first="Benoit" last="Beuselinck">Benoit Beuselinck</name><affiliation><nlm:aff id="af61"><institution>University Hospital Gasthuisberg</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</nlm:aff></affiliation></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name><affiliation><nlm:aff id="af37"><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name><affiliation><nlm:aff id="af37"><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Seibold, Petra" sort="Seibold, Petra" uniqKey="Seibold P" first="Petra" last="Seibold">Petra Seibold</name><affiliation><nlm:aff id="af37"><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Flesch Janys, Dieter" sort="Flesch Janys, Dieter" uniqKey="Flesch Janys D" first="Dieter" last="Flesch-Janys">Dieter Flesch-Janys</name><affiliation><nlm:aff wicri:cut=" and" id="af62"><addr-line>Department of Cancer Epidemiology/Clinical Cancer Registry</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af63"><addr-line>Institute for Medical Biometrics and Epidemiology</addr-line>,<institution>University Clinic Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Radice, Paolo" sort="Radice, Paolo" uniqKey="Radice P" first="Paolo" last="Radice">Paolo Radice</name><affiliation><nlm:aff wicri:cut=" and" id="af64"><addr-line>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine</addr-line></nlm:aff></affiliation></author><author><name sortKey="Peterlongo, Paolo" sort="Peterlongo, Paolo" uniqKey="Peterlongo P" first="Paolo" last="Peterlongo">Paolo Peterlongo</name><affiliation><nlm:aff id="af66"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation></author><author><name sortKey="Peissel, Bernard" sort="Peissel, Bernard" uniqKey="Peissel B" first="Bernard" last="Peissel">Bernard Peissel</name><affiliation><nlm:aff id="af65"><addr-line>Unit of Medical Genetics, Department of Preventive and Predictive Medicine</addr-line>,<institution>Fondazione IRCCS Istituto Nazionale dei Tumori (INT)</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation></author><author><name sortKey="Pensotti, Valeria" sort="Pensotti, Valeria" uniqKey="Pensotti V" first="Valeria" last="Pensotti">Valeria Pensotti</name><affiliation><nlm:aff id="af66"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af67"><institution>Cogentech Cancer Genetic Test Laboratory</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name><affiliation><nlm:aff wicri:cut=" and" id="af68"><addr-line>Department of Laboratory Medicine and Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Olson, Janet E" sort="Olson, Janet E" uniqKey="Olson J" first="Janet E." last="Olson">Janet E. Olson</name><affiliation><nlm:aff id="af69"><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Slettedahl, Seth" sort="Slettedahl, Seth" uniqKey="Slettedahl S" first="Seth" last="Slettedahl">Seth Slettedahl</name><affiliation><nlm:aff id="af69"><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Vachon, Celine" sort="Vachon, Celine" uniqKey="Vachon C" first="Celine" last="Vachon">Celine Vachon</name><affiliation><nlm:aff id="af69"><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af70"><addr-line>Cancer Epidemiology Centre</addr-line>,<institution>Cancer Council Victoria</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Milne, Roger L" sort="Milne, Roger L" uniqKey="Milne R" first="Roger L." last="Milne">Roger L. Milne</name><affiliation><nlm:aff wicri:cut=" and" id="af7"><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af70"><addr-line>Cancer Epidemiology Centre</addr-line>,<institution>Cancer Council Victoria</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Mclean, Catriona" sort="Mclean, Catriona" uniqKey="Mclean C" first="Catriona" last="Mclean">Catriona Mclean</name><affiliation><nlm:aff id="af71"><addr-line>Anatomical Pathology</addr-line>,<institution>The Alfred Hospital</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</nlm:aff></affiliation></author><author><name sortKey="Haiman, Christopher A" sort="Haiman, Christopher A" uniqKey="Haiman C" first="Christopher A." last="Haiman">Christopher A. Haiman</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Henderson, Brian E" sort="Henderson, Brian E" uniqKey="Henderson B" first="Brian E." last="Henderson">Brian E. Henderson</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Schumacher, Fredrick" sort="Schumacher, Fredrick" uniqKey="Schumacher F" first="Fredrick" last="Schumacher">Fredrick Schumacher</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name><affiliation><nlm:aff id="af73"><addr-line>Epidemiology Program, Cancer Research Center</addr-line>,<institution>University of Hawaii</institution>,<addr-line>Honolulu, HI</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Simard, Jacques" sort="Simard, Jacques" uniqKey="Simard J" first="Jacques" last="Simard">Jacques Simard</name><affiliation><nlm:aff id="af74"><addr-line>Cancer Genomics Laboratory</addr-line>,<institution>Centre Hospitalier Universitaire de Québec Research Center and Laval University</institution>,<addr-line>Quebec City, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Goldberg, Mark S" sort="Goldberg, Mark S" uniqKey="Goldberg M" first="Mark S." last="Goldberg">Mark S. Goldberg</name><affiliation><nlm:aff id="af75"><addr-line>Department of Medicine</addr-line>,<institution>McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af76"><addr-line>Division of Clinical Epidemiology</addr-line>,<institution>McGill University Health Centre, Royal Victoria Hospital</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Labreche, France" sort="Labreche, France" uniqKey="Labreche F" first="France" last="Labrèche">France Labrèche</name><affiliation><nlm:aff id="af77"><addr-line>Département de Médecine Sociale et Préventive, Département de Santé Environnementale et Santé au travail</addr-line>,<institution>Université de Montréal</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Dumont, Martine" sort="Dumont, Martine" uniqKey="Dumont M" first="Martine" last="Dumont">Martine Dumont</name><affiliation><nlm:aff id="af74"><addr-line>Cancer Genomics Laboratory</addr-line>,<institution>Centre Hospitalier Universitaire de Québec Research Center and Laval University</institution>,<addr-line>Quebec City, QC</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Kristensen, Vessela" sort="Kristensen, Vessela" uniqKey="Kristensen V" first="Vessela" last="Kristensen">Vessela Kristensen</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af79"><addr-line>Institute of Clinical Medicine</addr-line>,<institution>University of Oslo (UiO)</institution>,<addr-line>0450 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Aln S, Grethe Grenaker" sort="Aln S, Grethe Grenaker" uniqKey="Aln S G" first="Grethe Grenaker" last="Aln S">Grethe Grenaker Aln S</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Nord, Silje" sort="Nord, Silje" uniqKey="Nord S" first="Silje" last="Nord">Silje Nord</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Borresen Dale, Anne Lise" sort="Borresen Dale, Anne Lise" uniqKey="Borresen Dale A" first="Anne-Lise" last="Borresen-Dale">Anne-Lise Borresen-Dale</name><affiliation><nlm:aff id="af78"><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af79"><addr-line>Institute of Clinical Medicine</addr-line>,<institution>University of Oslo (UiO)</institution>,<addr-line>0450 Oslo</addr-line>,<country>Norway</country>,</nlm:aff></affiliation></author><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Deming Halverson, Sandra" sort="Deming Halverson, Sandra" uniqKey="Deming Halverson S" first="Sandra" last="Deming-Halverson">Sandra Deming-Halverson</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Shrubsole, Martha" sort="Shrubsole, Martha" uniqKey="Shrubsole M" first="Martha" last="Shrubsole">Martha Shrubsole</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Long, Jirong" sort="Long, Jirong" uniqKey="Long J" first="Jirong" last="Long">Jirong Long</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Winqvist, Robert" sort="Winqvist, Robert" uniqKey="Winqvist R" first="Robert" last="Winqvist">Robert Winqvist</name><affiliation><nlm:aff id="af81"><addr-line>Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Pylk S, Katri" sort="Pylk S, Katri" uniqKey="Pylk S K" first="Katri" last="Pylk S">Katri Pylk S</name><affiliation><nlm:aff id="af81"><addr-line>Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu</addr-line>,</nlm:aff></affiliation></author><author><name sortKey="Jukkola Vuorinen, Arja" sort="Jukkola Vuorinen, Arja" uniqKey="Jukkola Vuorinen A" first="Arja" last="Jukkola-Vuorinen">Arja Jukkola-Vuorinen</name><affiliation><nlm:aff wicri:cut=" and" id="af82"><addr-line>Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Grip, Mervi" sort="Grip, Mervi" uniqKey="Grip M" first="Mervi" last="Grip">Mervi Grip</name><affiliation><nlm:aff id="af83"><addr-line>Department of Surgery</addr-line>,<institution>Oulu University Hospital, University of Oulu</institution>,<addr-line>Oulu</addr-line>,<country>Finland</country>,</nlm:aff></affiliation></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name><affiliation><nlm:aff wicri:cut=" and" id="af84"><addr-line>Ontario Cancer Genetics Network</addr-line></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af86"><addr-line>Department of Molecular Genetics</addr-line></nlm:aff></affiliation></author><author><name sortKey="Knight, Julia A" sort="Knight, Julia A" uniqKey="Knight J" first="Julia A." last="Knight">Julia A. Knight</name><affiliation><nlm:aff id="af85"><addr-line>Prosserman Centre for Health Research</addr-line>,<institution>Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af87"><addr-line>Division of Epidemiology, Dalla Lana School of Public Health</addr-line>,<institution>University of Toronto</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name><affiliation><nlm:aff wicri:cut=" and" id="af84"><addr-line>Ontario Cancer Genetics Network</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tchatchou, Sandrine" sort="Tchatchou, Sandrine" uniqKey="Tchatchou S" first="Sandrine" last="Tchatchou">Sandrine Tchatchou</name><affiliation><nlm:aff id="af88"><institution>Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</nlm:aff></affiliation></author><author><name sortKey="Devilee, Peter" sort="Devilee, Peter" uniqKey="Devilee P" first="Peter" last="Devilee">Peter Devilee</name><affiliation><nlm:aff wicri:cut=" and" id="af89"><addr-line>Department of Human Genetics and Department of Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tollenaar, Robertus A E M" sort="Tollenaar, Robertus A E M" uniqKey="Tollenaar R" first="Robertus A. E. M." last="Tollenaar">Robertus A. E. M. Tollenaar</name><affiliation><nlm:aff id="af90"><addr-line>Department of Surgical Oncology</addr-line>,<institution>Leiden University Medical Center</institution>,<addr-line>2300 RC</addr-line>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Seynaeve, Caroline M" sort="Seynaeve, Caroline M" uniqKey="Seynaeve C" first="Caroline M." last="Seynaeve">Caroline M. Seynaeve</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Van Asperen, Christi J" sort="Van Asperen, Christi J" uniqKey="Van Asperen C" first="Christi J." last="Van Asperen">Christi J. Van Asperen</name><affiliation><nlm:aff id="af92"><addr-line>Department of Clinical Genetics</addr-line>,<institution>Leiden University Medical Center</institution>,<addr-line>P.O. Box 9600, 2300 RC</addr-line>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Garcia Closas, Montserrat" sort="Garcia Closas, Montserrat" uniqKey="Garcia Closas M" first="Montserrat" last="Garcia-Closas">Montserrat Garcia-Closas</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Figueroa, Jonine" sort="Figueroa, Jonine" uniqKey="Figueroa J" first="Jonine" last="Figueroa">Jonine Figueroa</name><affiliation><nlm:aff id="af93"><addr-line>Division of Cancer Epidemiology and Genetics</addr-line>,<institution>National Cancer Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J." last="Chanock">Stephen J. Chanock</name><affiliation><nlm:aff id="af93"><addr-line>Division of Cancer Epidemiology and Genetics</addr-line>,<institution>National Cancer Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Lissowska, Jolanta" sort="Lissowska, Jolanta" uniqKey="Lissowska J" first="Jolanta" last="Lissowska">Jolanta Lissowska</name><affiliation><nlm:aff id="af94"><addr-line>Department of Cancer Epidemiology and Prevention</addr-line>,<institution>M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology</institution>,<addr-line>Warsaw</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Czene, Kamila" sort="Czene, Kamila" uniqKey="Czene K" first="Kamila" last="Czene">Kamila Czene</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Darabi, Hatef" sort="Darabi, Hatef" uniqKey="Darabi H" first="Hatef" last="Darabi">Hatef Darabi</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Mikael" sort="Eriksson, Mikael" uniqKey="Eriksson M" first="Mikael" last="Eriksson">Mikael Eriksson</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Klevebring, Daniel" sort="Klevebring, Daniel" uniqKey="Klevebring D" first="Daniel" last="Klevebring">Daniel Klevebring</name><affiliation><nlm:aff id="af94"><addr-line>Department of Cancer Epidemiology and Prevention</addr-line>,<institution>M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology</institution>,<addr-line>Warsaw</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Hooning, Maartje J" sort="Hooning, Maartje J" uniqKey="Hooning M" first="Maartje J." last="Hooning">Maartje J. Hooning</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Hollestelle, Antoinette" sort="Hollestelle, Antoinette" uniqKey="Hollestelle A" first="Antoinette" last="Hollestelle">Antoinette Hollestelle</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Van Deurzen, Carolien H M" sort="Van Deurzen, Carolien H M" uniqKey="Van Deurzen C" first="Carolien H. M." last="Van Deurzen">Carolien H. M. Van Deurzen</name><affiliation><nlm:aff id="af96"><addr-line>Department of Pathology</addr-line>,<institution>Erasmus University Medical Center</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Kriege, Mieke" sort="Kriege, Mieke" uniqKey="Kriege M" first="Mieke" last="Kriege">Mieke Kriege</name><affiliation><nlm:aff id="af91"><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</nlm:aff></affiliation></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Li, Jingmei" sort="Li, Jingmei" uniqKey="Li J" first="Jingmei" last="Li">Jingmei Li</name><affiliation><nlm:aff id="af97"><addr-line>Human Genetics Division</addr-line>,<institution>Genome Institute of Singapore</institution>,<addr-line>Singapore 138672</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="af97"><addr-line>Human Genetics Division</addr-line>,<institution>Genome Institute of Singapore</institution>,<addr-line>Singapore 138672</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Humphreys, Keith" sort="Humphreys, Keith" uniqKey="Humphreys K" first="Keith" last="Humphreys">Keith Humphreys</name><affiliation><nlm:aff id="af95"><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</nlm:aff></affiliation></author><author><name sortKey="Cox, Angela" sort="Cox, Angela" uniqKey="Cox A" first="Angela" last="Cox">Angela Cox</name><affiliation><nlm:aff id="af98"><addr-line>Sheffield Cancer Research, Department of Oncology</addr-line>,<institution>University of Sheffield</institution>,<addr-line>Sheffield</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Cross, Simon S" sort="Cross, Simon S" uniqKey="Cross S" first="Simon S." last="Cross">Simon S. Cross</name><affiliation><nlm:aff id="af99"><addr-line>Academic Unit of Pathology, Department of Neuroscience</addr-line>,<institution>University of Sheffield</institution>,<addr-line>Sheffield</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Reed, Malcolm W R" sort="Reed, Malcolm W R" uniqKey="Reed M" first="Malcolm W. R." last="Reed">Malcolm W. R. Reed</name><affiliation><nlm:aff id="af100"><addr-line>Brighton and Sussex Medical School</addr-line>,<institution>University of Sussex</institution>,<addr-line>Brighton, East Sussex</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Pharoah, Paul D P" sort="Pharoah, Paul D P" uniqKey="Pharoah P" first="Paul D. P." last="Pharoah">Paul D. P. Pharoah</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dunning, Alison M" sort="Dunning, Alison M" uniqKey="Dunning A" first="Alison M." last="Dunning">Alison M. Dunning</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shah, Mitul" sort="Shah, Mitul" uniqKey="Shah M" first="Mitul" last="Shah">Mitul Shah</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Perkins, Barbara J" sort="Perkins, Barbara J" uniqKey="Perkins B" first="Barbara J." last="Perkins">Barbara J. Perkins</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Jakubowska, Anna" sort="Jakubowska, Anna" uniqKey="Jakubowska A" first="Anna" last="Jakubowska">Anna Jakubowska</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Lubinski, Jan" sort="Lubinski, Jan" uniqKey="Lubinski J" first="Jan" last="Lubinski">Jan Lubinski</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Jaworska Bieniek, Katarzyna" sort="Jaworska Bieniek, Katarzyna" uniqKey="Jaworska Bieniek K" first="Katarzyna" last="Jaworska-Bieniek">Katarzyna Jaworska-Bieniek</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Durda, Katarzyna" sort="Durda, Katarzyna" uniqKey="Durda K" first="Katarzyna" last="Durda">Katarzyna Durda</name><affiliation><nlm:aff id="af101"><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</nlm:aff></affiliation></author><author><name sortKey="Ashworth, Alan" sort="Ashworth, Alan" uniqKey="Ashworth A" first="Alan" last="Ashworth">Alan Ashworth</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Swerdlow, Anthony" sort="Swerdlow, Anthony" uniqKey="Swerdlow A" first="Anthony" last="Swerdlow">Anthony Swerdlow</name><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Jones, Michael" sort="Jones, Michael" uniqKey="Jones M" first="Michael" last="Jones">Michael Jones</name><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Schoemaker, Minouk J" sort="Schoemaker, Minouk J" uniqKey="Schoemaker M" first="Minouk J." last="Schoemaker">Minouk J. Schoemaker</name><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Meindl, Alfons" sort="Meindl, Alfons" uniqKey="Meindl A" first="Alfons" last="Meindl">Alfons Meindl</name><affiliation><nlm:aff id="af102"><addr-line>Division of Gynaecology and Obstetrics</addr-line>,<institution>Technische Universität München</institution>,<addr-line>81675 Munich</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Schmutzler, Rita K" sort="Schmutzler, Rita K" uniqKey="Schmutzler R" first="Rita K." last="Schmutzler">Rita K. Schmutzler</name><affiliation><nlm:aff id="af103"><addr-line>Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), Medical Faculty</addr-line>,<institution>University of Cologne and University Hospital Cologne</institution>,<addr-line>Cologne</addr-line>,<country>Germany</country>,</nlm:aff></affiliation></author><author><name sortKey="Olswold, Curtis" sort="Olswold, Curtis" uniqKey="Olswold C" first="Curtis" last="Olswold">Curtis Olswold</name><affiliation><nlm:aff wicri:cut=" and" id="af68"><addr-line>Department of Laboratory Medicine and Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Slager, Susan" sort="Slager, Susan" uniqKey="Slager S" first="Susan" last="Slager">Susan Slager</name><affiliation><nlm:aff wicri:cut=" and" id="af68"><addr-line>Department of Laboratory Medicine and Pathology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Toland, Amanda E" sort="Toland, Amanda E" uniqKey="Toland A" first="Amanda E." last="Toland">Amanda E. Toland</name><affiliation><nlm:aff id="af104"><addr-line>Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center</addr-line>,<institution>The Ohio State University</institution>,<addr-line>Columbus, OH</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Yannoukakos, Drakoulis" sort="Yannoukakos, Drakoulis" uniqKey="Yannoukakos D" first="Drakoulis" last="Yannoukakos">Drakoulis Yannoukakos</name><affiliation><nlm:aff id="af105"><addr-line>Molecular Diagnostics Laboratory</addr-line>,<institution>IRRP, National Centre for Scientific Research ‘Demokritos’, Aghia Paraskevi Attikis</institution>,<addr-line>Athens</addr-line>,<country>Greece</country>,</nlm:aff></affiliation></author><author><name sortKey="Muir, Kenneth" sort="Muir, Kenneth" uniqKey="Muir K" first="Kenneth" last="Muir">Kenneth Muir</name><affiliation><nlm:aff id="af106"><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af107"><addr-line>Institute of Population Health</addr-line>,<institution>University of Manchester</institution>,<addr-line>Manchester</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Lophatananon, Artitaya" sort="Lophatananon, Artitaya" uniqKey="Lophatananon A" first="Artitaya" last="Lophatananon">Artitaya Lophatananon</name><affiliation><nlm:aff id="af106"><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Stewart Brown, Sarah" sort="Stewart Brown, Sarah" uniqKey="Stewart Brown S" first="Sarah" last="Stewart-Brown">Sarah Stewart-Brown</name><affiliation><nlm:aff id="af106"><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Siriwanarangsan, Pornthep" sort="Siriwanarangsan, Pornthep" uniqKey="Siriwanarangsan P" first="Pornthep" last="Siriwanarangsan">Pornthep Siriwanarangsan</name><affiliation><nlm:aff id="af108"><institution>Ministry of Public Health</institution>,<addr-line>Nonthaburi</addr-line>,<country>Thailand</country>,</nlm:aff></affiliation></author><author><name sortKey="Matsuo, Keitaro" sort="Matsuo, Keitaro" uniqKey="Matsuo K" first="Keitaro" last="Matsuo">Keitaro Matsuo</name><affiliation><nlm:aff id="af109"><addr-line>Department of Preventive Medicine</addr-line>,<institution>Kyushu University Faculty of Medical Sciences</institution>,<addr-line>Fukuoka</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Ito, Hidema" sort="Ito, Hidema" uniqKey="Ito H" first="Hidema" last="Ito">Hidema Ito</name><affiliation><nlm:aff id="af110"><addr-line>Division of Epidemiology and Prevention</addr-line>,<institution>Aichi Cancer Center Research Institute</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Iwata, Hiroji" sort="Iwata, Hiroji" uniqKey="Iwata H" first="Hiroji" last="Iwata">Hiroji Iwata</name><affiliation><nlm:aff id="af111"><addr-line>Department of Breast Oncology</addr-line>,<institution>Aichi Cancer Center Hospital</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Ishiguro, Junko" sort="Ishiguro, Junko" uniqKey="Ishiguro J" first="Junko" last="Ishiguro">Junko Ishiguro</name><affiliation><nlm:aff id="af111"><addr-line>Department of Breast Oncology</addr-line>,<institution>Aichi Cancer Center Hospital</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</nlm:aff></affiliation></author><author><name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H." last="Wu">Anna H. Wu</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Tseng, Chiu Chen" sort="Tseng, Chiu Chen" uniqKey="Tseng C" first="Chiu-Chen" last="Tseng">Chiu-Chen Tseng</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Van Den Berg, David" sort="Van Den Berg, David" uniqKey="Van Den Berg D" first="David" last="Van Den Berg">David Van Den Berg</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Stram, Daniel O" sort="Stram, Daniel O" uniqKey="Stram D" first="Daniel O." last="Stram">Daniel O. Stram</name><affiliation><nlm:aff id="af72"><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Teo, Soo Hwang" sort="Teo, Soo Hwang" uniqKey="Teo S" first="Soo Hwang" last="Teo">Soo Hwang Teo</name><affiliation><nlm:aff id="af112"><addr-line>Cancer Research Initiatives Foundation</addr-line>,<institution>Sime Darby Medical Centre</institution>,<addr-line>Subang Jaya, Selangor</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af113"><addr-line>Breast Cancer Research Unit, University Malaya Cancer Research Institute</addr-line>,<institution>University Malaya Medical Centre</institution>,<addr-line>Kuala Lumpur</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation></author><author><name sortKey="Yip, Cheng Har" sort="Yip, Cheng Har" uniqKey="Yip C" first="Cheng Har" last="Yip">Cheng Har Yip</name><affiliation><nlm:aff id="af113"><addr-line>Breast Cancer Research Unit, University Malaya Cancer Research Institute</addr-line>,<institution>University Malaya Medical Centre</institution>,<addr-line>Kuala Lumpur</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation></author><author><name sortKey="Kang, Peter" sort="Kang, Peter" uniqKey="Kang P" first="Peter" last="Kang">Peter Kang</name><affiliation><nlm:aff id="af112"><addr-line>Cancer Research Initiatives Foundation</addr-line>,<institution>Sime Darby Medical Centre</institution>,<addr-line>Subang Jaya, Selangor</addr-line>,<country>Malaysia</country>,</nlm:aff></affiliation></author><author><name sortKey="Ikram, Mohammad Kamran" sort="Ikram, Mohammad Kamran" uniqKey="Ikram M" first="Mohammad Kamran" last="Ikram">Mohammad Kamran Ikram</name><affiliation><nlm:aff id="af114"><addr-line>Singapore Eye Research Institute</addr-line>,<institution>National University of Singapore</institution>,<addr-line>168751 Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Shu, Xiao Ou" sort="Shu, Xiao Ou" uniqKey="Shu X" first="Xiao-Ou" last="Shu">Xiao-Ou Shu</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name><affiliation><nlm:aff id="af115"><institution>Shanghai Center for Disease Control and Prevention</institution>,<addr-line>Shanghai</addr-line>,<country>China</country>,</nlm:aff></affiliation></author><author><name sortKey="Gao, Yu Tang" sort="Gao, Yu Tang" uniqKey="Gao Y" first="Yu-Tang" last="Gao">Yu-Tang Gao</name><affiliation><nlm:aff id="af116"><addr-line>Department of Epidemiology</addr-line>,<institution>Shanghai Cancer Institute</institution>,<addr-line>Shanghai</addr-line>,<country>China</country>,</nlm:aff></affiliation></author><author><name sortKey="Cai, Hui" sort="Cai, Hui" uniqKey="Cai H" first="Hui" last="Cai">Hui Cai</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Kang, Daehee" sort="Kang, Daehee" uniqKey="Kang D" first="Daehee" last="Kang">Daehee Kang</name><affiliation><nlm:aff wicri:cut=" and" id="af117"><addr-line>Department of Preventive Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af119"><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af120"><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Choi, Ji Yeob" sort="Choi, Ji Yeob" uniqKey="Choi J" first="Ji-Yeob" last="Choi">Ji-Yeob Choi</name><affiliation><nlm:aff id="af119"><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af120"><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Park, Sue K" sort="Park, Sue K" uniqKey="Park S" first="Sue K." last="Park">Sue K. Park</name><affiliation><nlm:aff wicri:cut=" and" id="af117"><addr-line>Department of Preventive Medicine</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af119"><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af120"><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Noh, Dong Young" sort="Noh, Dong Young" uniqKey="Noh D" first="Dong-Young" last="Noh">Dong-Young Noh</name><affiliation><nlm:aff id="af118"><addr-line>Department of Surgery</addr-line>,<institution>Seoul National University College of Medicine</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</nlm:aff></affiliation></author><author><name sortKey="Hartman, Mikael" sort="Hartman, Mikael" uniqKey="Hartman M" first="Mikael" last="Hartman">Mikael Hartman</name><affiliation><nlm:aff wicri:cut=" and" id="af121"><addr-line>Saw Swee Hock School of Public Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af122"><addr-line>Department of Surgery, Yong Loo Lin School of Medicine</addr-line>,<institution>National University of Singapore</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af123"><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Miao, Hui" sort="Miao, Hui" uniqKey="Miao H" first="Hui" last="Miao">Hui Miao</name><affiliation><nlm:aff wicri:cut=" and" id="af121"><addr-line>Saw Swee Hock School of Public Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af123"><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Lim, Wei Yen" sort="Lim, Wei Yen" uniqKey="Lim W" first="Wei Yen" last="Lim">Wei Yen Lim</name><affiliation><nlm:aff wicri:cut=" and" id="af121"><addr-line>Saw Swee Hock School of Public Health</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af123"><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Lee, Soo Chin" sort="Lee, Soo Chin" uniqKey="Lee S" first="Soo Chin" last="Lee">Soo Chin Lee</name><affiliation><nlm:aff id="af124"><addr-line>Department of Haematology-Oncology</addr-line>,<institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af125"><addr-line>Cancer Science Institute of Singapore</addr-line>,<institution>National University Singapore</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</nlm:aff></affiliation></author><author><name sortKey="Sangrajrang, Suleeporn" sort="Sangrajrang, Suleeporn" uniqKey="Sangrajrang S" first="Suleeporn" last="Sangrajrang">Suleeporn Sangrajrang</name><affiliation><nlm:aff id="af126"><institution>National Cancer Institute</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country>,</nlm:aff></affiliation></author><author><name sortKey="Gaborieau, Valerie" sort="Gaborieau, Valerie" uniqKey="Gaborieau V" first="Valerie" last="Gaborieau">Valerie Gaborieau</name><affiliation><nlm:aff id="af127"><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Brennan, Paul" sort="Brennan, Paul" uniqKey="Brennan P" first="Paul" last="Brennan">Paul Brennan</name><affiliation><nlm:aff id="af127"><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Mckay, James" sort="Mckay, James" uniqKey="Mckay J" first="James" last="Mckay">James Mckay</name><affiliation><nlm:aff id="af127"><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</nlm:aff></affiliation></author><author><name sortKey="Wu, Pei Ei" sort="Wu, Pei Ei" uniqKey="Wu P" first="Pei-Ei" last="Wu">Pei-Ei Wu</name><affiliation><nlm:aff wicri:cut=" and" id="af128"><addr-line>Taiwan Biobank</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af129"><addr-line>Institute of Biomedical Sciences</addr-line>,<institution>Academia Sinica</institution>,<addr-line>Taipei 115</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Hou, Ming Feng" sort="Hou, Ming Feng" uniqKey="Hou M" first="Ming-Feng" last="Hou">Ming-Feng Hou</name><affiliation><nlm:aff id="af130"><addr-line>Cancer Center and Department of Surgery</addr-line>,<institution>Kaohsiung Medical University Chung-Ho Memorial Hospital</institution>,<addr-line>Kaohsiung 804</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Yu, Jyh Cherng" sort="Yu, Jyh Cherng" uniqKey="Yu J" first="Jyh-Cherng" last="Yu">Jyh-Cherng Yu</name><affiliation><nlm:aff id="af131"><addr-line>Department of Surgery</addr-line>,<institution>Tri-Service General Hospital and National Defense Medical Center</institution>,<addr-line>Taipei 114</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Shen, Chen Yang" sort="Shen, Chen Yang" uniqKey="Shen C" first="Chen-Yang" last="Shen">Chen-Yang Shen</name><affiliation><nlm:aff id="af130"><addr-line>Cancer Center and Department of Surgery</addr-line>,<institution>Kaohsiung Medical University Chung-Ho Memorial Hospital</institution>,<addr-line>Kaohsiung 804</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af132"><addr-line>School of Public Health</addr-line>,<institution>China Medical University</institution>,<addr-line>Taichung 404</addr-line>,<country>Taiwan</country>,</nlm:aff></affiliation></author><author><name sortKey="Blot, William" sort="Blot, William" uniqKey="Blot W" first="William" last="Blot">William Blot</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation><affiliation><nlm:aff id="af133"><institution>International Epidemiology Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Cai, Qiuyin" sort="Cai, Qiuyin" uniqKey="Cai Q" first="Qiuyin" last="Cai">Qiuyin Cai</name><affiliation><nlm:aff id="af80"><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Signorello, Lisa B" sort="Signorello, Lisa B" uniqKey="Signorello L" first="Lisa B." last="Signorello">Lisa B. Signorello</name><affiliation><nlm:aff id="af134"><institution>Dana-Farber/Harvard Cancer Center</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af135"><addr-line>Department of Epidemiology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Luccarini, Craig" sort="Luccarini, Craig" uniqKey="Luccarini C" first="Craig" last="Luccarini">Craig Luccarini</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bayes, Caroline" sort="Bayes, Caroline" uniqKey="Bayes C" first="Caroline" last="Bayes">Caroline Bayes</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ahmed, Shahana" sort="Ahmed, Shahana" uniqKey="Ahmed S" first="Shahana" last="Ahmed">Shahana Ahmed</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Maranian, Mel" sort="Maranian, Mel" uniqKey="Maranian M" first="Mel" last="Maranian">Mel Maranian</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Healey, Catherine S" sort="Healey, Catherine S" uniqKey="Healey C" first="Catherine S." last="Healey">Catherine S. Healey</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gonzalez Neira, Anna" sort="Gonzalez Neira, Anna" uniqKey="Gonzalez Neira A" first="Anna" last="González-Neira">Anna González-Neira</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Pita, Guillermo" sort="Pita, Guillermo" uniqKey="Pita G" first="Guillermo" last="Pita">Guillermo Pita</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Alonso, M Rosario" sort="Alonso, M Rosario" uniqKey="Alonso M" first="M. Rosario" last="Alonso">M. Rosario Alonso</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Alvarez, Nuria" sort="Alvarez, Nuria" uniqKey="Alvarez N" first="Nuria" last="Álvarez">Nuria Álvarez</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Herrero, Daniel" sort="Herrero, Daniel" uniqKey="Herrero D" first="Daniel" last="Herrero">Daniel Herrero</name><affiliation><nlm:aff wicri:cut=" and" id="af137"><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Tessier, Daniel C" sort="Tessier, Daniel C" uniqKey="Tessier D" first="Daniel C." last="Tessier">Daniel C. Tessier</name><affiliation><nlm:aff id="af138"><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Vincent, Daniel" sort="Vincent, Daniel" uniqKey="Vincent D" first="Daniel" last="Vincent">Daniel Vincent</name><affiliation><nlm:aff id="af138"><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Bacot, Francois" sort="Bacot, Francois" uniqKey="Bacot F" first="Francois" last="Bacot">Francois Bacot</name><affiliation><nlm:aff id="af138"><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="af136"><addr-line>Program in Molecular and Genetic Epidemiology</addr-line>,<institution>Harvard School of Public Health</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindstrom">Sara Lindstrom</name><affiliation><nlm:aff id="af136"><addr-line>Program in Molecular and Genetic Epidemiology</addr-line>,<institution>Harvard School of Public Health</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</nlm:aff></affiliation></author><author><name sortKey="Dennis, Joe" sort="Dennis, Joe" uniqKey="Dennis J" first="Joe" last="Dennis">Joe Dennis</name><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Michailidou, Kyriaki" sort="Michailidou, Kyriaki" uniqKey="Michailidou K" first="Kyriaki" last="Michailidou">Kyriaki Michailidou</name><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Bolla, Manjeet K" sort="Bolla, Manjeet K" uniqKey="Bolla M" first="Manjeet K." last="Bolla">Manjeet K. Bolla</name><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F." last="Easton">Douglas F. Easton</name><affiliation><nlm:aff wicri:cut=" and" id="af5"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af6"><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Dos Santos Silva, Isabel" sort="Dos Santos Silva, Isabel" uniqKey="Dos Santos Silva I" first="Isabel" last="Dos Santos Silva">Isabel Dos Santos Silva</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author><author><name sortKey="Fletcher, Olivia" sort="Fletcher, Olivia" uniqKey="Fletcher O" first="Olivia" last="Fletcher">Olivia Fletcher</name><affiliation><nlm:aff id="af1"><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=" and" id="af2"><addr-line>Division of Breast Cancer Research</addr-line></nlm:aff></affiliation></author><author><name sortKey="Peto, Julian" sort="Peto, Julian" uniqKey="Peto J" first="Julian" last="Peto">Julian Peto</name><affiliation><nlm:aff id="af4"><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</nlm:aff></affiliation></author></analytic><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88–0.92]; <italic>P</italic>-value = 1.58 × 10<sup>−25</sup>). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08–1.17]; <italic>P</italic>-value = 7.89 × 10<sup>−09</sup>) and rs13294895 (OR = 1.09 [1.06–1.12]; <italic>P</italic>-value = 2.97 × 10<sup>−11</sup>). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06–1.18]; <italic>P</italic>-value = 2.77 × 10<sup>−05</sup>). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. <italic>In vitro</italic> analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the <italic>KLF4</italic> gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Shin, H R" uniqKey="Shin H">H.R. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Hum Mol Genet</journal-id><journal-id journal-id-type="iso-abbrev">Hum. Mol. Genet</journal-id><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-id journal-id-type="hwp">hmg</journal-id><journal-title-group><journal-title>Human Molecular Genetics</journal-title></journal-title-group><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25652398</article-id><article-id pub-id-type="pmc">4406292</article-id><article-id pub-id-type="doi">10.1093/hmg/ddv035</article-id><article-id pub-id-type="publisher-id">ddv035</article-id><article-categories><subj-group subj-group-type="heading"><subject>Association Studies Articles</subject></subj-group></article-categories><title-group><article-title>Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2</article-title></title-group><contrib-group><contrib 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ref-type="aff" rid="af116">116</xref></contrib><contrib contrib-type="author"><name><surname>Cai</surname><given-names>Hui</given-names></name><xref ref-type="aff" rid="af80">80</xref></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Daehee</given-names></name><xref ref-type="aff" rid="af117">117</xref><xref ref-type="aff" rid="af119">119</xref><xref ref-type="aff" rid="af120">120</xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Ji-Yeob</given-names></name><xref ref-type="aff" rid="af119">119</xref><xref ref-type="aff" rid="af120">120</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Sue K.</given-names></name><xref ref-type="aff" rid="af117">117</xref><xref ref-type="aff" rid="af119">119</xref><xref ref-type="aff" rid="af120">120</xref></contrib><contrib contrib-type="author"><name><surname>Noh</surname><given-names>Dong-Young</given-names></name><xref ref-type="aff" rid="af118">118</xref></contrib><contrib contrib-type="author"><name><surname>Hartman</surname><given-names>Mikael</given-names></name><xref ref-type="aff" rid="af121">121</xref><xref ref-type="aff" rid="af122">122</xref><xref ref-type="aff" rid="af123">123</xref></contrib><contrib contrib-type="author"><name><surname>Miao</surname><given-names>Hui</given-names></name><xref ref-type="aff" rid="af121">121</xref><xref ref-type="aff" rid="af123">123</xref></contrib><contrib contrib-type="author"><name><surname>Lim</surname><given-names>Wei Yen</given-names></name><xref ref-type="aff" rid="af121">121</xref><xref ref-type="aff" rid="af123">123</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Soo Chin</given-names></name><xref ref-type="aff" rid="af124">124</xref><xref ref-type="aff" rid="af125">125</xref></contrib><contrib contrib-type="author"><name><surname>Sangrajrang</surname><given-names>Suleeporn</given-names></name><xref ref-type="aff" rid="af126">126</xref></contrib><contrib contrib-type="author"><name><surname>Gaborieau</surname><given-names>Valerie</given-names></name><xref ref-type="aff" rid="af127">127</xref></contrib><contrib contrib-type="author"><name><surname>Brennan</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="af127">127</xref></contrib><contrib contrib-type="author"><name><surname>Mckay</surname><given-names>James</given-names></name><xref ref-type="aff" rid="af127">127</xref></contrib><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Pei-Ei</given-names></name><xref ref-type="aff" rid="af128">128</xref><xref ref-type="aff" rid="af129">129</xref></contrib><contrib contrib-type="author"><name><surname>Hou</surname><given-names>Ming-Feng</given-names></name><xref ref-type="aff" rid="af130">130</xref></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Jyh-Cherng</given-names></name><xref ref-type="aff" rid="af131">131</xref></contrib><contrib contrib-type="author"><name><surname>Shen</surname><given-names>Chen-Yang</given-names></name><xref ref-type="aff" rid="af130">130</xref><xref ref-type="aff" rid="af132">132</xref></contrib><contrib contrib-type="author"><name><surname>Blot</surname><given-names>William</given-names></name><xref ref-type="aff" rid="af80">80</xref><xref ref-type="aff" rid="af133">133</xref></contrib><contrib contrib-type="author"><name><surname>Cai</surname><given-names>Qiuyin</given-names></name><xref ref-type="aff" rid="af80">80</xref></contrib><contrib contrib-type="author"><name><surname>Signorello</surname><given-names>Lisa B.</given-names></name><xref ref-type="aff" rid="af134">134</xref><xref ref-type="aff" rid="af135">135</xref></contrib><contrib contrib-type="author"><name><surname>Luccarini</surname><given-names>Craig</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Bayes</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Ahmed</surname><given-names>Shahana</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Maranian</surname><given-names>Mel</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Healey</surname><given-names>Catherine S.</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>González-Neira</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="af137">137</xref></contrib><contrib contrib-type="author"><name><surname>Pita</surname><given-names>Guillermo</given-names></name><xref ref-type="aff" rid="af137">137</xref></contrib><contrib contrib-type="author"><name><surname>Alonso</surname><given-names>M. Rosario</given-names></name><xref ref-type="aff" rid="af137">137</xref></contrib><contrib contrib-type="author"><name><surname>Álvarez</surname><given-names>Nuria</given-names></name><xref ref-type="aff" rid="af137">137</xref></contrib><contrib contrib-type="author"><name><surname>Herrero</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="af137">137</xref></contrib><contrib contrib-type="author"><name><surname>Tessier</surname><given-names>Daniel C.</given-names></name><xref ref-type="aff" rid="af138">138</xref></contrib><contrib contrib-type="author"><name><surname>Vincent</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="af138">138</xref></contrib><contrib contrib-type="author"><name><surname>Bacot</surname><given-names>Francois</given-names></name><xref ref-type="aff" rid="af138">138</xref></contrib><contrib contrib-type="author"><name><surname>Hunter</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="af136">136</xref></contrib><contrib contrib-type="author"><name><surname>Lindstrom</surname><given-names>Sara</given-names></name><xref ref-type="aff" rid="af136">136</xref></contrib><contrib contrib-type="author"><name><surname>Dennis</surname><given-names>Joe</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Michailidou</surname><given-names>Kyriaki</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Bolla</surname><given-names>Manjeet K.</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Easton</surname><given-names>Douglas F.</given-names></name><xref ref-type="aff" rid="af5">5</xref><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>dos Santos Silva</surname><given-names>Isabel</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Fletcher</surname><given-names>Olivia</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Peto</surname><given-names>Julian</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><aff id="af1"><label>1</label><addr-line>The Breakthrough Breast Cancer</addr-line><addr-line>Research Centre</addr-line>,</aff><aff id="af2"><label>2</label><addr-line>Division of Breast Cancer Research</addr-line> and</aff><aff id="af3"><label>3</label><addr-line>Division of Genetics and Epidemiology</addr-line>,<institution>The Institute of Cancer Research</institution>,<addr-line>London</addr-line>,<country>UK</country>,</aff><aff id="af4"><label>4</label><addr-line>Department of Non-Communicable Disease</addr-line><addr-line>Epidemiology</addr-line>,<institution>London School of Hygiene and Tropical Medicine</institution>,<addr-line>London</addr-line>,<country>UK</country>,</aff><aff id="af5"><label>5</label><addr-line>Centre for Cancer Genetic Epidemiology, Department of Oncology</addr-line> and</aff><aff id="af6"><label>6</label><addr-line>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care</addr-line>,<institution>University of Cambridge</institution>,<addr-line>Cambridge</addr-line>,<country>UK</country>,</aff><aff id="af7"><label>7</label><addr-line>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health</addr-line> and</aff><aff id="af8"><label>8</label><addr-line>Department of Pathology</addr-line>,<institution>The University of Melbourne</institution>,<addr-line>Melbourne, VIC 3010</addr-line>,<country>Australia</country>,</aff><aff id="af9"><label>9</label><addr-line>Centre for Genetic Origins of Health and Disease</addr-line>,<institution>University of Western Australia</institution>,<addr-line>Perth, WA</addr-line>,<country>Australia</country>,</aff><aff id="af10"><label>10</label><addr-line>Netherlands Cancer Institute</addr-line>,<institution>Antoni van Leeuwenhoek Hospital</institution>,<addr-line>1066 CX Amsterdam</addr-line>,<country>The Netherlands</country>,</aff><aff id="af11"><label>11</label><addr-line>University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen</addr-line> and</aff><aff id="af12"><label>12</label><addr-line>Institute of Human Genetics, University Hospital Erlangen</addr-line>,<institution>Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN</institution>,<addr-line>91054 Erlangen</addr-line>,<country>Germany</country>,</aff><aff id="af13"><label>13</label><addr-line>David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology</addr-line>,<institution>University of California at Los Angeles</institution>,<addr-line>Los Angeles, CA 90095</addr-line>,<country>USA</country>,</aff><aff id="af14"><label>14</label><addr-line>Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine</addr-line> and</aff><aff id="af15"><label>15</label><addr-line>NIHR Barts Cardiovascular Biomedical Research Unit</addr-line>,<institution>Queen Mary University of London</institution>,<addr-line>London</addr-line>,<country>UK</country>,</aff><aff id="af16"><label>16</label><addr-line>Division of Cancer Studies</addr-line>,<institution>Kings College London, Guy's Hospital</institution>,<addr-line>London</addr-line>,<country>UK</country>,</aff><aff id="af17"><label>17</label><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre</addr-line>,<institution>University of Oxford</institution>,<country>UK</country>,</aff><aff id="af18"><label>18</label><addr-line>Clinical Science Institute</addr-line>,<institution>University Hospital Galway</institution>,<addr-line>Galway</addr-line>,<country>Ireland</country>,</aff><aff id="af19"><label>19</label><addr-line>Department of Obstetrics and Gynecology</addr-line> and</aff><aff id="af20"><label>20</label><addr-line>National Center for Tumor Diseases</addr-line>,<institution>University of Heidelberg</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</aff><aff id="af21"><label>21</label><addr-line>Molecular Epidemiology Group</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>69120 Heidelberg</addr-line>,<country>Germany</country>,</aff><aff id="af22"><label>22</label><addr-line>Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018</addr-line>,<institution>Environmental Epidemiology of Cancer</institution>,<addr-line>Villejuif</addr-line>,<country>France</country>,</aff><aff id="af23"><label>23</label><institution>University Paris-Sud</institution>,<addr-line>UMRS 1018, Villejuif</addr-line>,<country>France</country>,</aff><aff id="af24"><label>24</label><addr-line>Copenhagen General Population Study</addr-line> and</aff><aff id="af25"><label>25</label><addr-line>Department of Clinical Biochemistry</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>2730 Herlev</addr-line>,<country>Denmark</country>,</aff><aff id="af26"><label>26</label><addr-line>Department of Breast Surgery</addr-line>,<institution>Herlev Hospital, Copenhagen University Hospital</institution>,<addr-line>Copenhagen</addr-line>,<country>Denmark</country>,</aff><aff id="af27"><label>27</label><addr-line>Human Genetics Group, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>28029 Madrid</addr-line>,<country>Spain</country>,</aff><aff id="af28"><label>28</label><institution>Centro de Investigación en Red de Enfermedades Raras (CIBERER)</institution>,<addr-line>46010 Valencia</addr-line>,<country>Spain</country>,</aff><aff id="af29"><label>29</label><addr-line>Servicio de Oncología Médica</addr-line>,<institution>Hospital Universitario La Paz</institution>,<addr-line>28046 Madrid</addr-line>,<country>Spain</country>,</aff><aff id="af30"><label>30</label><addr-line>Servicio de Cirugía General y Especialidades</addr-line> and</aff><aff id="af31"><label>31</label><addr-line>Servicio de Anatomía Patológica</addr-line>,<institution>Hospital Monte Naranco</institution>,<addr-line>33012 Oviedo</addr-line>,<country>Spain</country>,</aff><aff id="af32"><label>32</label><addr-line>Department of Epidemiology</addr-line>,<institution>University of California Irvine</institution>,<addr-line>Irvine, CA</addr-line>,<country>USA</country>,</aff><aff id="af33"><label>33</label><institution>Beckman Research Institute of City of Hope</institution>,<addr-line>Duarte, CA</addr-line>,<country>USA</country>,</aff><aff id="af34"><label>34</label><addr-line>Division of Clinical Epidemiology and Aging Research</addr-line>,</aff><aff id="af35"><label>35</label><addr-line>German Cancer Consortium (DKTK)</addr-line>,</aff><aff id="af36"><label>36</label><addr-line>Molecular Genetics of Breast Cancer</addr-line> and</aff><aff id="af37"><label>37</label><addr-line>Division of Cancer Epidemiology</addr-line>,<institution>German Cancer Research Center (DKFZ)</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country>,</aff><aff id="af38"><label>38</label><institution>Saarland Cancer Registry</institution>,<addr-line>Saarbrücken</addr-line>,<country>Germany</country>,</aff><aff id="af39"><label>39</label><institution>Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology</institution>,<addr-line>Stuttgart</addr-line>,<country>Germany</country>,</aff><aff id="af40"><label>40</label><institution>University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country>,</aff><aff id="af41"><label>41</label><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr—University Bochum (IPA)</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country>,</aff><aff id="af42"><label>42</label><addr-line>Department of Internal Medicine</addr-line>,<institution>Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</aff><aff id="af43"><label>43</label><addr-line>Institute of Pathology</addr-line>,<institution>Medical Faculty of the University of Bonn</institution>,<addr-line>Bonn</addr-line>,<country>Germany</country>,</aff><aff id="af44"><label>44</label><addr-line>Institute of Occupational Medicine and Maritime Medicine</addr-line>,<institution>University Medical Center Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country>,</aff><aff id="af45"><label>45</label><addr-line>Department of Obstetrics and Gynecology</addr-line>,</aff><aff id="af46"><label>46</label><addr-line>Department of Clinical Genetics</addr-line> and</aff><aff id="af47"><label>47</label><addr-line>Department of Oncology</addr-line>,<institution>University of Helsinki and Helsinki University Hospital</institution>,<addr-line>Helsinki</addr-line>,<country>Finland</country>,</aff><aff id="af48"><label>48</label><addr-line>Department of Radiation Oncology</addr-line> and</aff><aff id="af49"><label>49</label><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Hannover Medical School</institution>,<addr-line>Hannover</addr-line>,<country>Germany</country>,</aff><aff id="af50"><label>50</label><addr-line>Department of Molecular Medicine and Surgery</addr-line> and</aff><aff id="af51"><label>51</label><addr-line>Department of Oncology-Pathology</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm</addr-line>,<country>Sweden</country>,</aff><aff id="af52"><label>52</label><addr-line>School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine</addr-line> and</aff><aff id="af53"><label>53</label><addr-line>School of Medicine, Institute of Clinical Medicine, Oncology</addr-line>,<institution>University of Eastern Finland</institution>,<addr-line>Kuopio</addr-line>,<country>Finland</country>,</aff><aff id="af54"><label>54</label><addr-line>Imaging Center, Department of Clinical Pathology</addr-line> and</aff><aff id="af55"><label>55</label><addr-line>Biocenter Kuopio, Cancer Center of Eastern Finland</addr-line>,<institution>Kuopio University Hospital</institution>,<addr-line>Kuopio</addr-line>,<country>Finland</country>,</aff><aff id="af56"><label>56</label><addr-line>Central Finland Health Care District</addr-line>,<institution>Jyväskylä Central Hospital</institution>,<addr-line>Jyväskylä</addr-line>,<country>Finland</country>,</aff><aff id="af57"><label>57</label><institution>QIMR Berghofer Medical Research Institute</institution>,<addr-line>Brisbane, QLD</addr-line>,<country>Australia</country>,</aff><aff id="af58"><label>58</label><institution>Peter MacCallum Cancer Center</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</aff><aff id="af59"><label>59</label><addr-line>Vesalius Research Center (VRC)</addr-line>,<institution>VIB</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</aff><aff id="af60"><label>60</label><addr-line>Laboratory for Translational Genetics, Department of Oncology</addr-line>,<institution>University of Leuven</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</aff><aff id="af61"><label>61</label><institution>University Hospital Gasthuisberg</institution>,<addr-line>Leuven</addr-line>,<country>Belgium</country>,</aff><aff id="af62"><label>62</label><addr-line>Department of Cancer Epidemiology/Clinical Cancer Registry</addr-line> and</aff><aff id="af63"><label>63</label><addr-line>Institute for Medical Biometrics and Epidemiology</addr-line>,<institution>University Clinic Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country>,</aff><aff id="af64"><label>64</label><addr-line>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine</addr-line> and</aff><aff id="af65"><label>65</label><addr-line>Unit of Medical Genetics, Department of Preventive and Predictive Medicine</addr-line>,<institution>Fondazione IRCCS Istituto Nazionale dei Tumori (INT)</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</aff><aff id="af66"><label>66</label><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</aff><aff id="af67"><label>67</label><institution>Cogentech Cancer Genetic Test Laboratory</institution>,<addr-line>Milan</addr-line>,<country>Italy</country>,</aff><aff id="af68"><label>68</label><addr-line>Department of Laboratory Medicine and Pathology</addr-line> and</aff><aff id="af69"><label>69</label><addr-line>Department of Health Sciences Research</addr-line>,<institution>Mayo Clinic</institution>,<addr-line>Rochester, MN</addr-line>,<country>USA</country>,</aff><aff id="af70"><label>70</label><addr-line>Cancer Epidemiology Centre</addr-line>,<institution>Cancer Council Victoria</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</aff><aff id="af71"><label>71</label><addr-line>Anatomical Pathology</addr-line>,<institution>The Alfred Hospital</institution>,<addr-line>Melbourne, VIC</addr-line>,<country>Australia</country>,</aff><aff id="af72"><label>72</label><addr-line>Department of Preventive Medicine, Keck School of Medicine</addr-line>,<institution>University of Southern California</institution>,<addr-line>Los Angeles, CA</addr-line>,<country>USA</country>,</aff><aff id="af73"><label>73</label><addr-line>Epidemiology Program, Cancer Research Center</addr-line>,<institution>University of Hawaii</institution>,<addr-line>Honolulu, HI</addr-line>,<country>USA</country>,</aff><aff id="af74"><label>74</label><addr-line>Cancer Genomics Laboratory</addr-line>,<institution>Centre Hospitalier Universitaire de Québec Research Center and Laval University</institution>,<addr-line>Quebec City, QC</addr-line>,<country>Canada</country>,</aff><aff id="af75"><label>75</label><addr-line>Department of Medicine</addr-line>,<institution>McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</aff><aff id="af76"><label>76</label><addr-line>Division of Clinical Epidemiology</addr-line>,<institution>McGill University Health Centre, Royal Victoria Hospital</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</aff><aff id="af77"><label>77</label><addr-line>Département de Médecine Sociale et Préventive, Département de Santé Environnementale et Santé au travail</addr-line>,<institution>Université de Montréal</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country>,</aff><aff id="af78"><label>78</label><addr-line>Department of Genetics</addr-line>,<institution>Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet</institution>,<addr-line>N-0310 Oslo</addr-line>,<country>Norway</country>,</aff><aff id="af79"><label>79</label><addr-line>Institute of Clinical Medicine</addr-line>,<institution>University of Oslo (UiO)</institution>,<addr-line>0450 Oslo</addr-line>,<country>Norway</country>,</aff><aff id="af80"><label>80</label><addr-line>Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center</addr-line>,<institution>Vanderbilt University School of Medicine</institution>,<addr-line>Nashville, TN</addr-line>,<country>USA</country>,</aff><aff id="af81"><label>81</label><addr-line>Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics and Biocenter Oulu</addr-line>,</aff><aff id="af82"><label>82</label><addr-line>Department of Oncology</addr-line> and</aff><aff id="af83"><label>83</label><addr-line>Department of Surgery</addr-line>,<institution>Oulu University Hospital, University of Oulu</institution>,<addr-line>Oulu</addr-line>,<country>Finland</country>,</aff><aff id="af84"><label>84</label><addr-line>Ontario Cancer Genetics Network</addr-line> and</aff><aff id="af85"><label>85</label><addr-line>Prosserman Centre for Health Research</addr-line>,<institution>Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</aff><aff id="af86"><label>86</label><addr-line>Department of Molecular Genetics</addr-line> and</aff><aff id="af87"><label>87</label><addr-line>Division of Epidemiology, Dalla Lana School of Public Health</addr-line>,<institution>University of Toronto</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</aff><aff id="af88"><label>88</label><institution>Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital</institution>,<addr-line>Toronto, ON</addr-line>,<country>Canada</country>,</aff><aff id="af89"><label>89</label><addr-line>Department of Human Genetics and Department of Pathology</addr-line> and</aff><aff id="af90"><label>90</label><addr-line>Department of Surgical Oncology</addr-line>,<institution>Leiden University Medical Center</institution>,<addr-line>2300 RC</addr-line>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country>,</aff><aff id="af91"><label>91</label><addr-line>Department of Medical Oncology, Family Cancer Clinic</addr-line>,<institution>Erasmus MC Cancer Institute</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</aff><aff id="af92"><label>92</label><addr-line>Department of Clinical Genetics</addr-line>,<institution>Leiden University Medical Center</institution>,<addr-line>P.O. Box 9600, 2300 RC</addr-line>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country>,</aff><aff id="af93"><label>93</label><addr-line>Division of Cancer Epidemiology and Genetics</addr-line>,<institution>National Cancer Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</aff><aff id="af94"><label>94</label><addr-line>Department of Cancer Epidemiology and Prevention</addr-line>,<institution>M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology</institution>,<addr-line>Warsaw</addr-line>,<country>Poland</country>,</aff><aff id="af95"><label>95</label><addr-line>Department of Medical Epidemiology and Biostatistics</addr-line>,<institution>Karolinska Institutet</institution>,<addr-line>Stockholm 17177</addr-line>,<country>Sweden</country>,</aff><aff id="af96"><label>96</label><addr-line>Department of Pathology</addr-line>,<institution>Erasmus University Medical Center</institution>,<addr-line>Rotterdam</addr-line>,<country>The Netherlands</country>,</aff><aff id="af97"><label>97</label><addr-line>Human Genetics Division</addr-line>,<institution>Genome Institute of Singapore</institution>,<addr-line>Singapore 138672</addr-line>,<country>Singapore</country>,</aff><aff id="af98"><label>98</label><addr-line>Sheffield Cancer Research, Department of Oncology</addr-line>,<institution>University of Sheffield</institution>,<addr-line>Sheffield</addr-line>,<country>UK</country>,</aff><aff id="af99"><label>99</label><addr-line>Academic Unit of Pathology, Department of Neuroscience</addr-line>,<institution>University of Sheffield</institution>,<addr-line>Sheffield</addr-line>,<country>UK</country>,</aff><aff id="af100"><label>100</label><addr-line>Brighton and Sussex Medical School</addr-line>,<institution>University of Sussex</institution>,<addr-line>Brighton, East Sussex</addr-line>,<country>UK</country>,</aff><aff id="af101"><label>101</label><addr-line>Department of Genetics and Pathology</addr-line>,<institution>Pomeranian Medical University</institution>,<addr-line>70-115 Szczecin</addr-line>,<country>Poland</country>,</aff><aff id="af102"><label>102</label><addr-line>Division of Gynaecology and Obstetrics</addr-line>,<institution>Technische Universität München</institution>,<addr-line>81675 Munich</addr-line>,<country>Germany</country>,</aff><aff id="af103"><label>103</label><addr-line>Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), Medical Faculty</addr-line>,<institution>University of Cologne and University Hospital Cologne</institution>,<addr-line>Cologne</addr-line>,<country>Germany</country>,</aff><aff id="af104"><label>104</label><addr-line>Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center</addr-line>,<institution>The Ohio State University</institution>,<addr-line>Columbus, OH</addr-line>,<country>USA</country>,</aff><aff id="af105"><label>105</label><addr-line>Molecular Diagnostics Laboratory</addr-line>,<institution>IRRP, National Centre for Scientific Research ‘Demokritos’, Aghia Paraskevi Attikis</institution>,<addr-line>Athens</addr-line>,<country>Greece</country>,</aff><aff id="af106"><label>106</label><addr-line>Division of Health Sciences, Warwick Medical School</addr-line>,<institution>Warwick University</institution>,<addr-line>Coventry</addr-line>,<country>UK</country>,</aff><aff id="af107"><label>107</label><addr-line>Institute of Population Health</addr-line>,<institution>University of Manchester</institution>,<addr-line>Manchester</addr-line>,<country>UK</country>,</aff><aff id="af108"><label>108</label><institution>Ministry of Public Health</institution>,<addr-line>Nonthaburi</addr-line>,<country>Thailand</country>,</aff><aff id="af109"><label>109</label><addr-line>Department of Preventive Medicine</addr-line>,<institution>Kyushu University Faculty of Medical Sciences</institution>,<addr-line>Fukuoka</addr-line>,<country>Japan</country>,</aff><aff id="af110"><label>110</label><addr-line>Division of Epidemiology and Prevention</addr-line>,<institution>Aichi Cancer Center Research Institute</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</aff><aff id="af111"><label>111</label><addr-line>Department of Breast Oncology</addr-line>,<institution>Aichi Cancer Center Hospital</institution>,<addr-line>Nagoya</addr-line>,<country>Japan</country>,</aff><aff id="af112"><label>112</label><addr-line>Cancer Research Initiatives Foundation</addr-line>,<institution>Sime Darby Medical Centre</institution>,<addr-line>Subang Jaya, Selangor</addr-line>,<country>Malaysia</country>,</aff><aff id="af113"><label>113</label><addr-line>Breast Cancer Research Unit, University Malaya Cancer Research Institute</addr-line>,<institution>University Malaya Medical Centre</institution>,<addr-line>Kuala Lumpur</addr-line>,<country>Malaysia</country>,</aff><aff id="af114"><label>114</label><addr-line>Singapore Eye Research Institute</addr-line>,<institution>National University of Singapore</institution>,<addr-line>168751 Singapore</addr-line>,<country>Singapore</country>,</aff><aff id="af115"><label>115</label><institution>Shanghai Center for Disease Control and Prevention</institution>,<addr-line>Shanghai</addr-line>,<country>China</country>,</aff><aff id="af116"><label>116</label><addr-line>Department of Epidemiology</addr-line>,<institution>Shanghai Cancer Institute</institution>,<addr-line>Shanghai</addr-line>,<country>China</country>,</aff><aff id="af117"><label>117</label><addr-line>Department of Preventive Medicine</addr-line> and</aff><aff id="af118"><label>118</label><addr-line>Department of Surgery</addr-line>,<institution>Seoul National University College of Medicine</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</aff><aff id="af119"><label>119</label><addr-line>Department of Biomedical Sciences</addr-line>,<institution>Seoul National University Graduate School</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</aff><aff id="af120"><label>120</label><addr-line>Cancer Research Institute</addr-line>,<institution>Seoul National University</institution>,<addr-line>Seoul</addr-line>,<country>Korea</country>,</aff><aff id="af121"><label>121</label><addr-line>Saw Swee Hock School of Public Health</addr-line> and</aff><aff id="af122"><label>122</label><addr-line>Department of Surgery, Yong Loo Lin School of Medicine</addr-line>,<institution>National University of Singapore</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</aff><aff id="af123"><label>123</label><institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</aff><aff id="af124"><label>124</label><addr-line>Department of Haematology-Oncology</addr-line>,<institution>National University Health System</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</aff><aff id="af125"><label>125</label><addr-line>Cancer Science Institute of Singapore</addr-line>,<institution>National University Singapore</institution>,<addr-line>Singapore</addr-line>,<country>Singapore</country>,</aff><aff id="af126"><label>126</label><institution>National Cancer Institute</institution>,<addr-line>Bangkok</addr-line>,<country>Thailand</country>,</aff><aff id="af127"><label>127</label><institution>International Agency for Research on Cancer</institution>,<addr-line>Lyon</addr-line>,<country>France</country>,</aff><aff id="af128"><label>128</label><addr-line>Taiwan Biobank</addr-line> and</aff><aff id="af129"><label>129</label><addr-line>Institute of Biomedical Sciences</addr-line>,<institution>Academia Sinica</institution>,<addr-line>Taipei 115</addr-line>,<country>Taiwan</country>,</aff><aff id="af130"><label>130</label><addr-line>Cancer Center and Department of Surgery</addr-line>,<institution>Kaohsiung Medical University Chung-Ho Memorial Hospital</institution>,<addr-line>Kaohsiung 804</addr-line>,<country>Taiwan</country>,</aff><aff id="af131"><label>131</label><addr-line>Department of Surgery</addr-line>,<institution>Tri-Service General Hospital and National Defense Medical Center</institution>,<addr-line>Taipei 114</addr-line>,<country>Taiwan</country>,</aff><aff id="af132"><label>132</label><addr-line>School of Public Health</addr-line>,<institution>China Medical University</institution>,<addr-line>Taichung 404</addr-line>,<country>Taiwan</country>,</aff><aff id="af133"><label>133</label><institution>International Epidemiology Institute</institution>,<addr-line>Rockville, MD</addr-line>,<country>USA</country>,</aff><aff id="af134"><label>134</label><institution>Dana-Farber/Harvard Cancer Center</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</aff><aff id="af135"><label>135</label><addr-line>Department of Epidemiology</addr-line> and</aff><aff id="af136"><label>136</label><addr-line>Program in Molecular and Genetic Epidemiology</addr-line>,<institution>Harvard School of Public Health</institution>,<addr-line>Boston, MA</addr-line>,<country>USA</country>,</aff><aff id="af137"><label>137</label><addr-line>Human Genotyping-CEGEN Unit, Human Cancer Genetics Program</addr-line>,<institution>Spanish National Cancer Research Centre (CNIO)</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country> and</aff><aff id="af138"><label>138</label><institution>Centre d'innovation Génome Québec et Université McGill</institution>,<addr-line>Montréal, QC</addr-line>,<country>Canada</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed at: Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. Tel: +44 2071535330; Email: <email>nicholas.orr@icr.ac.uk</email></corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>04</day><month>2</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>04</day><month>2</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>24</volume><issue>10</issue><fpage>2966</fpage><lpage>2984</lpage><history><date date-type="received"><day>22</day><month>12</month><year>2014</year></date><date date-type="accepted"><day>30</day><month>1</month><year>2015</year></date></history><permissions><copyright-statement>© The Author 2015. Published by Oxford University Press.</copyright-statement><copyright-year>2015</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="ddv035.pdf"></self-uri><abstract><p>We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88–0.92]; <italic>P</italic>-value = 1.58 × 10<sup>−25</sup>). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08–1.17]; <italic>P</italic>-value = 7.89 × 10<sup>−09</sup>) and rs13294895 (OR = 1.09 [1.06–1.12]; <italic>P</italic>-value = 2.97 × 10<sup>−11</sup>). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06–1.18]; <italic>P</italic>-value = 2.77 × 10<sup>−05</sup>). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. <italic>In vitro</italic> analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the <italic>KLF4</italic> gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.</p></abstract></article-meta></front><body><sec sec-type="intro" id="s1"><title>Introduction</title><p>Breast cancer is the most common female cancer worldwide, in both developed and less developed regions, including Asia and Africa. An estimated 1.38 million new breast cancer cases were diagnosed worldwide in 2008, and this burden is likely to increase in the coming decades as a result of population ageing and adoption of western lifestyles (<xref rid="DDV035C1" ref-type="bibr">1</xref>).</p><p>Susceptibility to breast cancer involves contributions from genetic, environmental, lifestyle and hormonal factors. Pathogenic mutations in the DNA-repair genes <italic>BRCA1</italic> and <italic>BRCA2</italic> confer high lifetime risks of the disease and are responsible for the majority of cases that occur in families with many affected members but account for only 20% of the excess familial relative risk (FRR) of the disease (<xref rid="DDV035C2" ref-type="bibr">2</xref>). Rare germline variants in genes including <italic>CHEK2</italic>, <italic>PALB2</italic> and <italic>ATM</italic> each confer moderately increased relative risks (RR) of breast cancer but make only small contributions to the excess FRR (<xref rid="DDV035C3" ref-type="bibr">3</xref>–<xref rid="DDV035C5" ref-type="bibr">5</xref>). Genome-wide association studies (GWAS) have identified 79 single nucleotide polymorphisms (SNPs) that influence breast cancer susceptibility and explain a further 15% of the FRR (<xref rid="DDV035C6" ref-type="bibr">6</xref>–<xref rid="DDV035C19" ref-type="bibr">19</xref>). Statistical modelling suggests that several thousands of additional breast cancer susceptibility SNPs remain undetected (<xref rid="DDV035C9" ref-type="bibr">9</xref>). Genetic variants can be incorporated into risk prediction models that can stratify women by level of risk. The power of such models will improve as more variants are identified (<xref rid="DDV035C20" ref-type="bibr">20</xref>). One productive approach to identifying additional susceptibility variants is through fine-mapping of regions known to harbour susceptibility alleles.</p><p>The 9q31.2 breast cancer susceptibility locus, delineated by rs865686, was identified by a GWAS that utilised genetically enriched cases from the UK with either bilateral breast cancer or with a family history of the disease (<xref rid="DDV035C7" ref-type="bibr">7</xref>). A replication study using samples from the Breast Cancer Association Consortium (BCAC) indicated that the association with rs865686 was restricted to estrogen-receptor (ER) positive breast cancer (<xref rid="DDV035C21" ref-type="bibr">21</xref>). SNP rs865686 localises to a gene desert and consequently the mechanism of association is assumed to be through long-range regulation of target gene expression. The nearest neighbouring genes to rs865686 include Kruppel-like factor 4 (<italic>KLF4</italic>), RAD23 homologue B (<italic>RAD23B</italic>; both >600 kb proximal), actin-like 7B (<italic>ACTL7B</italic>) and inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein (<italic>IKBKAP</italic>; both >700 kb distal).</p><p>We performed a fine-mapping study, using over 85 000 European and 12 000 Asian ancestry samples from BCAC, in order to localise the causal variant underlying the association between rs865686 and susceptibility to breast cancer. In addition we assessed whether other independent breast cancer susceptibility SNPs could be detected at the 9q31.2 locus.</p></sec><sec sec-type="results" id="s2"><title>Results</title><p>We successfully genotyped a total of 424 SNPs spanning 110 740 582–111 100 826 bp (NCBI HG37) on chromosome 9. These SNPs captured ∼94% and 86% of common 1000 Genomes Project (1KGP) variants at <italic>r</italic><sup>2</sup> ≥ 0.8 in European and Asian populations, respectively. Association analyses were performed using 85 760 subjects of European ancestry, 12 491 subjects of Asian ancestry and 1978 subjects of African ancestry (<ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S1</ext-link>). We report only the results from the European and Asian studies, as there were too few samples for meaningful analyses of women of African ancestry. However, the full results from the European, Asian and African studies are presented in <ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S2</ext-link>A–C. We used statistical imputation of unobserved genotypes to increase the density of our fine-mapping analysis; a total of 2035 SNPs and insertion/deletion (indel) polymorphisms were inferred using 1000 Genomes Project (1KGP) reference data, from which 1529 variants were imputed with high certainty (Impute2 (<xref rid="DDV035C22" ref-type="bibr">22</xref>) information measure ≥0.5) and included in subsequent association analyses. Because no imputed variant was more significantly associated with breast cancer risk than the highest ranked, directly genotyped SNPs, they were not considered in the following analyses unless explicitly stated.</p><p>The most significantly associated SNP was rs676256 (odds ratio [OR] = 0.90 [0.88–0.92]; <italic>P</italic> = 1.58 × 10<sup>−25</sup>; Fig. <xref ref-type="fig" rid="DDV035F1">1</xref>A and Table <xref ref-type="table" rid="DDV035TB1">1</xref>; <ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S2</ext-link>A). SNP rs676256 was one of a 14.4 kb cluster of 38 genotyped or imputed correlated SNPs (<italic>r</italic><sup>2</sup> > 0.8 in controls of European ancestry) that also included SNP rs865686. Of the 38 SNPs correlated with rs676256 at <italic>r</italic><sup>2</sup> ≥ 0.8, 27 had likelihood ratios >1:100 relative to rs676256 (<ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S3</ext-link>); hence it is likely that at least one of the 28 SNPs in this independent set of correlated highly associated variants (iCHAV) is causal (<xref rid="DDV035C23" ref-type="bibr">23</xref>).
<table-wrap id="DDV035TB1" position="float"><label>Table 1.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with risk of breast cancer amongst women of European and Asian ancestry</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Population</th><th align="left" rowspan="1" colspan="1">Control MAF</th><th align="center" colspan="3" rowspan="1">Control genotype counts<hr></hr></th><th align="left" rowspan="1" colspan="1">Case MAF</th><th align="center" colspan="3" rowspan="1">Case genotype counts<hr></hr></th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>a</sup></th><th align="left" rowspan="1" colspan="1">OR<sup>b</sup></th><th align="left" rowspan="1" colspan="1">95% CI<sup>b</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">AA</td><td rowspan="1" colspan="1">AG</td><td rowspan="1" colspan="1">GG</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">AA</td><td rowspan="1" colspan="1">AG</td><td rowspan="1" colspan="1">GG</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">9q31.2</td><td rowspan="1" colspan="1">Caucasians</td><td rowspan="1" colspan="1">0.06</td><td rowspan="1" colspan="1">37579</td><td rowspan="1" colspan="1">4851</td><td rowspan="1" colspan="1">169</td><td rowspan="1" colspan="1">0.07</td><td rowspan="1" colspan="1">37 434</td><td rowspan="1" colspan="1">5560</td><td rowspan="1" colspan="1">164</td><td rowspan="1" colspan="1">7.89 × 10<sup>−09</sup></td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.08–1.17</td></tr><tr><td rowspan="1" colspan="1">110 837 073</td><td rowspan="1" colspan="1">Asians</td><td rowspan="1" colspan="1">0.38</td><td rowspan="1" colspan="1">2633</td><td rowspan="1" colspan="1">2976</td><td rowspan="1" colspan="1">1013</td><td rowspan="1" colspan="1">0.42</td><td rowspan="1" colspan="1">2023</td><td rowspan="1" colspan="1">2714</td><td rowspan="1" colspan="1">1057</td><td rowspan="1" colspan="1">2.77 × 10<sup>−05</sup></td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.06–1.18</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">GG</td><td rowspan="1" colspan="1">AG</td><td rowspan="1" colspan="1">AA</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">GG</td><td rowspan="1" colspan="1">AG</td><td rowspan="1" colspan="1">AA</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">9q31.2</td><td rowspan="1" colspan="1">Caucasians</td><td rowspan="1" colspan="1">0.20</td><td rowspan="1" colspan="1">28 954</td><td rowspan="1" colspan="1">12 372</td><td rowspan="1" colspan="1">1272</td><td rowspan="1" colspan="1">0.19</td><td rowspan="1" colspan="1">28 625</td><td rowspan="1" colspan="1">13 029</td><td rowspan="1" colspan="1">1506</td><td rowspan="1" colspan="1">2.97 × 10<sup>−11</sup></td><td rowspan="1" colspan="1">1.09</td><td rowspan="1" colspan="1">1.06–1.12</td></tr><tr><td rowspan="1" colspan="1">110 837 176</td><td rowspan="1" colspan="1">Asians</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">6244</td><td rowspan="1" colspan="1">372</td><td rowspan="1" colspan="1">8</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">5495</td><td rowspan="1" colspan="1">288</td><td rowspan="1" colspan="1">10</td><td rowspan="1" colspan="1">0.66</td><td rowspan="1" colspan="1">1.04</td><td rowspan="1" colspan="1">0.89–1.21</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">AA</td><td rowspan="1" colspan="1">AG</td><td rowspan="1" colspan="1">GG</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">AA</td><td rowspan="1" colspan="1">AG</td><td rowspan="1" colspan="1">GG</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">9q31.2</td><td rowspan="1" colspan="1">Caucasians</td><td rowspan="1" colspan="1">0.38</td><td rowspan="1" colspan="1">16166</td><td rowspan="1" colspan="1">20183</td><td rowspan="1" colspan="1">6250</td><td rowspan="1" colspan="1">0.36</td><td rowspan="1" colspan="1">18 011</td><td rowspan="1" colspan="1">19 670</td><td rowspan="1" colspan="1">5472</td><td rowspan="1" colspan="1">1.58 × 10<sup>−25</sup></td><td rowspan="1" colspan="1">0.90</td><td rowspan="1" colspan="1">0.88–0.92</td></tr><tr><td rowspan="1" colspan="1">110 895 353</td><td rowspan="1" colspan="1">Asians</td><td rowspan="1" colspan="1">0.05</td><td rowspan="1" colspan="1">6036</td><td rowspan="1" colspan="1">567</td><td rowspan="1" colspan="1">21</td><td rowspan="1" colspan="1">0.04</td><td rowspan="1" colspan="1">5329</td><td rowspan="1" colspan="1">455</td><td rowspan="1" colspan="1">11</td><td rowspan="1" colspan="1">0.3</td><td rowspan="1" colspan="1">0.94</td><td rowspan="1" colspan="1">0.82–1.06</td></tr></tbody></table><table-wrap-foot><fn id="TN1"><p><sup>a</sup><italic>P</italic>-values from single SNP test of association, computed from a likelihood-ratio test with one degree-of-freedom.</p></fn><fn id="TN2"><p><sup>b</sup>Odds ratios and 95% confidence intervals for SNP association with breast cancer estimated using logistic regression, adjusting for study and significant principal components and assuming multiplicativity on the odds scale for heterozygote and minor-allele homozygote ORs.</p></fn></table-wrap-foot></table-wrap><fig id="DDV035F1" position="float"><label>Figure 1.</label><caption><p>Regional association plots for 9q31.2 fine-mapping SNPs in European and Asian ancestry individuals. (<bold>A</bold>–<bold>D</bold>) Individual steps from a forward stepwise regression analysis using data from the Caucasian studies, in which the most strongly associated SNP from a given model is included as a covariate in the subsequent model. Chromosome position is indicated on the <italic>x</italic>-axis, and –log<sub>10</sub><italic>P</italic>-value on the <italic>y</italic>-axis. The models represented are adjusted for study and seven ancestry-informative principal components. Each directly genotyped SNP is represented as a single red diamond and the most significant SNP that attained genome-wide significance from each step of the stepwise regression is indicated by a yellow diamond. (<bold>E</bold>) Regional association plot for the 9q31.2 fine-mapping SNPs in subjects with Asian ancestry tested using a model adjusted for study and two ancestry-informative principal components.</p></caption><graphic xlink:href="ddv03501"></graphic></fig></p><p>To determine whether additional SNPs at 9q31.2 confer risks of breast cancer independently of rs676256, we fitted a series of stepwise logistic regression models (Fig. <xref ref-type="fig" rid="DDV035F1">1</xref>B–D), stopping when no additional SNPs reached genome-wide significance (Fig. <xref ref-type="fig" rid="DDV035F1">1</xref>D). We identified SNPs rs10816625 (stepwise OR = 1.12 [1.07–1.16]; <italic>P</italic> = 3.49 × 10<sup>−08</sup>; Fig. <xref ref-type="fig" rid="DDV035F1">1</xref>B) and rs13294895 (stepwise OR = 1.08 [1.06–1.11]; <italic>P</italic> = 4.56 × 10<sup>−10</sup>; Fig. <xref ref-type="fig" rid="DDV035F1">1</xref>C). The <italic>P</italic>-values and effect estimates for all three susceptibility SNPs, adjusted by study and ancestry-informative principal components, but not adjusted for the other SNPs, are shown in Table <xref ref-type="table" rid="DDV035TB1">1</xref>. All three SNPs remained strongly associated with breast cancer risk when modelled jointly (rs10816625: OR = 1.13 [1.09–1.18]; <italic>P</italic> = 5.04 × 10<sup>−10</sup>; rs13294895: OR = 1.08 [1.06–1.11]; <italic>P</italic> = 4.80 × 10<sup>−10</sup>; rs676256: OR = 0.91 [0.89–0.93]; <italic>P</italic> = 2.31 × 10<sup>−21</sup>). There was little evidence of between-study effect heterogeneity for each SNP (rs10816625: Cochran's Q <italic>P</italic>-value = 0.48, <italic>I</italic><sup>2</sup> = 0; rs13294895: Cochran's Q <italic>P</italic>-value = 0.86, <italic>I</italic><sup>2</sup> = 0; rs676256: Cochran's Q <italic>P</italic>-value = 0.27, <italic>I</italic><sup>2</sup> = 0.11). rs676256 is essentially uncorrelated with either rs10816625 or rs13294895 (rs676256|rs10816625: <italic>r</italic><sup>2</sup> = 2.5 × 10<sup>−04</sup>, <italic>D</italic>′ = 0.08; rs676256|rs13294895: <italic>r</italic><sup>2</sup> = 0.013, <italic>D</italic>′ = 0.31). rs10816625 and rs13294895, which are within 103 bp of each other, lie in the same LD block (<italic>D</italic>′ = 1). The risk alleles rarely occur together: analysis of computationally phased genotype data estimated only 160 haplotypes carrying the risk alleles of both rs10816625 and rs13294895 from a total of over 183 000, corresponding to an estimated population frequency of 0.09% (compared with 1.2% expected under equilibrium). However, given the relative rarity of the risk alleles, there is little correlation between the SNPs (<italic>r</italic><sup>2</sup> = 0.014). SNPs rs10816625 and rs13294895 were uncorrelated with any other variant at <italic>r</italic><sup>2</sup> ≥ 0.8.</p><p>In Asians, rs10816625 was notable for being the only SNP that showed evidence of association with breast cancer risk, albeit not at genome-wide levels of significance (OR = 1.12 [1.06–1.18]; <italic>P</italic> = 2.77 × 10<sup>−05</sup>; Fig. <xref ref-type="fig" rid="DDV035F1">1</xref>E and Table <xref ref-type="table" rid="DDV035TB1">1</xref>; <ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S2</ext-link>B). SNP rs10816625 has a relatively low minor-allele frequency (MAF; 6%) in European populations but is common in Asian populations (MAF averaged across controls from nine Asian studies = 38%). There was no evidence of inter-study heterogeneity for rs10816625 in the contributing Asian studies (Cochran's Q <italic>P</italic>-value = 0.51, <italic>I</italic><sup>2</sup> = 0). Although SNPs rs676256 (OR = 0.94 [0.82–1.06]; <italic>P</italic> = 0.3; Table <xref ref-type="table" rid="DDV035TB1">1</xref>), rs865686 (OR = 0.93 [0.84–1.02]; <italic>P</italic> = 0.13) and rs13294895 (OR = 1.04 [0.89–1.21]; <italic>P</italic> = 0.66) were not significantly associated with breast cancer risk in the Asian studies, their OR estimates were consistent with those of European women; power to detect associations of these SNPs was low because the minor allele frequencies were much lower than for Europeans. No SNPs were significantly associated with breast cancer risk in the African studies (<ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S2</ext-link>C).</p><p>All three SNPs were associated with ER-positive (rs10816625: OR = 1.14 [1.09–1.19], <italic>P</italic> = 2.39 × 10<sup>−08</sup>; rs13294895: OR = 1.11 [1.08–1.14], <italic>P</italic> = 3.54 × 10<sup>−12</sup>; rs676256: OR = 0.87 [0.85–0.89], <italic>P</italic> = 1.66 × 10<sup>−30</sup>; Table <xref ref-type="table" rid="DDV035TB2">2</xref>) but not ER-negative (rs10816625: OR = 1.04 [0.96–1.13], <italic>P</italic> = 0.29, <italic>P</italic><sub>het</sub> = 0.05; rs13294895: OR = 1.03 [0.98–1.08], <italic>P</italic> = 0.25, <italic>P</italic><sub>het</sub> = 0.003; rs676256: OR = 0.98 [0.94–1.02], <italic>P</italic> = 0.31, <italic>P</italic><sub>het</sub> = 2.08 × 10<sup>−08</sup>; Table <xref ref-type="table" rid="DDV035TB2">2</xref>) breast cancer in subjects with European ancestry. A similar pattern was observed for progesterone receptor (PR) expression, with the exception that SNP rs676256 also showed a nominally significant association with PR-negative tumours (OR = 0.95 [0.91–0.98], <italic>P</italic> = 0.002; Table <xref ref-type="table" rid="DDV035TB2">2</xref>). Because tumour ER and PR status are strongly correlated, we modelled ER and PR co-expression using polytomous logistic regression. This revealed a similar association between rs676256 and risk of ER-positive/PR-positive breast cancer (OR = 0.87 [0.84–0.89]; <italic>P</italic> = 1.33 × 10<sup>−24</sup>; Table <xref ref-type="table" rid="DDV035TB3">3</xref>), ER-positive/PR-negative breast cancer (OR = 0.90 [0.86–0.95]; <italic>P</italic> = 1.20 × 10<sup>−04</sup>) and ER-negative/PR-positive breast cancer (OR = 0.89 [0.80–1.00]; <italic>P</italic> = 0.04). We further explored the association of rs676256 with ER-negative/PR-positive breast cancer using case-only analysis for PR, adjusted for ER (<italic>P</italic> = 0.06). SNP rs10816625 was significantly associated with only ER-positive/PR-positive breast cancer; rs13294895 was significantly associated with ER-positive/PR-positive breast cancer and nominally associated with ER-positive/PR-negative disease (Table <xref ref-type="table" rid="DDV035TB3">3</xref>).
<table-wrap id="DDV035TB2" position="float"><label>Table 2.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with risk of breast cancer in European and Asian women stratified by ER status, PR status and HER2 status</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Population</th><th align="left" rowspan="1" colspan="1">Controls</th><th align="left" rowspan="1" colspan="1">Cases</th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1"><italic>P</italic><sub>het</sub><sup>c</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Caucasian</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" align="left" rowspan="1">ER+ tumours</td><td colspan="3" align="left" rowspan="1">ER− tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">41 324</td><td rowspan="1" colspan="1">25 851 | 6128</td><td rowspan="1" colspan="1">1.14</td><td rowspan="1" colspan="1">1.09–1.19</td><td rowspan="1" colspan="1">2.39 × 10<sup>−08</sup></td><td rowspan="1" colspan="1">1.04</td><td rowspan="1" colspan="1">0.96–1.13</td><td rowspan="1" colspan="1">0.29</td><td rowspan="1" colspan="1">0.05</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">41 323</td><td rowspan="1" colspan="1">25 851 | 6130</td><td rowspan="1" colspan="1">1.11</td><td rowspan="1" colspan="1">1.08–1.14</td><td rowspan="1" colspan="1">3.54 × 10<sup>−12</sup></td><td rowspan="1" colspan="1">1.03</td><td rowspan="1" colspan="1">0.98–1.08</td><td rowspan="1" colspan="1">0.25</td><td rowspan="1" colspan="1">0.003</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">41 324</td><td rowspan="1" colspan="1">25 847 | 6128</td><td rowspan="1" colspan="1">0.87</td><td rowspan="1" colspan="1">0.85–0.89</td><td rowspan="1" colspan="1">1.66 × 10<sup>−30</sup></td><td rowspan="1" colspan="1">0.98</td><td rowspan="1" colspan="1">0.94–1.02</td><td rowspan="1" colspan="1">0.31</td><td rowspan="1" colspan="1">2.08 × 10<sup>−08</sup></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" rowspan="1">PR+ tumours</td><td colspan="3" align="left" rowspan="1">PR− tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">41 618</td><td rowspan="1" colspan="1">19 207 | 8470</td><td rowspan="1" colspan="1">1.16</td><td rowspan="1" colspan="1">1.10–1.22</td><td rowspan="1" colspan="1">1.36 × 10<sup>−08</sup></td><td rowspan="1" colspan="1">1.06</td><td rowspan="1" colspan="1">0.99–1.13</td><td rowspan="1" colspan="1">0.11</td><td rowspan="1" colspan="1">0.02</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">41 617</td><td rowspan="1" colspan="1">19 207 | 8472</td><td rowspan="1" colspan="1">1.11</td><td rowspan="1" colspan="1">1.08–1.15</td><td rowspan="1" colspan="1">1.74 × 10<sup>−10</sup></td><td rowspan="1" colspan="1">1.05</td><td rowspan="1" colspan="1">1.00–1.10</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">0.01</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">41 619</td><td rowspan="1" colspan="1">19 207 | 8472</td><td rowspan="1" colspan="1">0.87</td><td rowspan="1" colspan="1">0.84–0.89</td><td rowspan="1" colspan="1">2.15 × 10<sup>−27</sup></td><td rowspan="1" colspan="1">0.95</td><td rowspan="1" colspan="1">0.91–0.98</td><td rowspan="1" colspan="1">0.002</td><td rowspan="1" colspan="1">2.73 × 10<sup>−06</sup></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" rowspan="1">HER2− tumours</td><td colspan="3" align="left" rowspan="1">HER2+ tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">31 756</td><td rowspan="1" colspan="1">12 872 | 2503</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">1.04–1.17</td><td rowspan="1" colspan="1">0.002</td><td rowspan="1" colspan="1">1.21</td><td rowspan="1" colspan="1">1.08–1.35</td><td rowspan="1" colspan="1">9.66 × 10<sup>−04</sup></td><td rowspan="1" colspan="1">0.09</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">31 755</td><td rowspan="1" colspan="1">12 874 | 2503</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">1.06–1.14</td><td rowspan="1" colspan="1">3.29 × 10<sup>−06</sup></td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">1.00–1.16</td><td rowspan="1" colspan="1">0.06</td><td rowspan="1" colspan="1">0.53</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">31 756</td><td rowspan="1" colspan="1">12 869 | 2502</td><td rowspan="1" colspan="1">0.87</td><td rowspan="1" colspan="1">0.85–0.90</td><td rowspan="1" colspan="1">2.75 × 10<sup>−16</sup></td><td rowspan="1" colspan="1">0.92</td><td rowspan="1" colspan="1">0.87–0.98</td><td rowspan="1" colspan="1">0.008</td><td rowspan="1" colspan="1">0.14</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Asian</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" align="left" rowspan="1">ER+ tumours</td><td colspan="3" align="left" rowspan="1">ER− tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6622</td><td rowspan="1" colspan="1">3183 | 1547</td><td rowspan="1" colspan="1">1.13</td><td rowspan="1" colspan="1">1.06–1.21</td><td rowspan="1" colspan="1">1.30 × 10<sup>−04</sup></td><td rowspan="1" colspan="1">1.14</td><td rowspan="1" colspan="1">1.05–1.24</td><td rowspan="1" colspan="1">0.002</td><td rowspan="1" colspan="1">0.84</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6624</td><td rowspan="1" colspan="1">3183 | 1546</td><td rowspan="1" colspan="1">1.04</td><td rowspan="1" colspan="1">0.87–1.26</td><td rowspan="1" colspan="1">0.65</td><td rowspan="1" colspan="1">0.92</td><td rowspan="1" colspan="1">0.71–1.18</td><td rowspan="1" colspan="1">0.5</td><td rowspan="1" colspan="1">0.25</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6624</td><td rowspan="1" colspan="1">3184 | 1547</td><td rowspan="1" colspan="1">0.94</td><td rowspan="1" colspan="1">0.80–1.10</td><td rowspan="1" colspan="1">0.42</td><td rowspan="1" colspan="1">0.98</td><td rowspan="1" colspan="1">0.80–1.19</td><td rowspan="1" colspan="1">0.82</td><td rowspan="1" colspan="1">0.76</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" rowspan="1">PR+ tumours</td><td colspan="3" align="left" rowspan="1">PR− tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">5733</td><td rowspan="1" colspan="1">2711 | 1621</td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.04–1.20</td><td rowspan="1" colspan="1">0.0012</td><td rowspan="1" colspan="1">1.15</td><td rowspan="1" colspan="1">1.06–1.25</td><td rowspan="1" colspan="1">5.45 × 10<sup>−04</sup></td><td rowspan="1" colspan="1">0.5</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">5753</td><td rowspan="1" colspan="1">2711 | 1621</td><td rowspan="1" colspan="1">1.04</td><td rowspan="1" colspan="1">0.85–1.27</td><td rowspan="1" colspan="1">0.72</td><td rowspan="1" colspan="1">0.98</td><td rowspan="1" colspan="1">0.77–1.25</td><td rowspan="1" colspan="1">0.88</td><td rowspan="1" colspan="1">0.55</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">5735</td><td rowspan="1" colspan="1">2712 | 1621</td><td rowspan="1" colspan="1">1.01</td><td rowspan="1" colspan="1">0.86–1.19</td><td rowspan="1" colspan="1">0.89</td><td rowspan="1" colspan="1">0.85</td><td rowspan="1" colspan="1">0.69–1.05</td><td rowspan="1" colspan="1">0.14</td><td rowspan="1" colspan="1">0.15</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" rowspan="1">HER2– tumours</td><td colspan="3" align="left" rowspan="1">HER2+ tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3852</td><td rowspan="1" colspan="1">1058 | 785</td><td rowspan="1" colspan="1">1.17</td><td rowspan="1" colspan="1">1.05–1.30</td><td rowspan="1" colspan="1">0.0032</td><td rowspan="1" colspan="1">1.17</td><td rowspan="1" colspan="1">1.04–1.32</td><td rowspan="1" colspan="1">0.01</td><td rowspan="1" colspan="1">0.78</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3853</td><td rowspan="1" colspan="1">1057 | 784</td><td rowspan="1" colspan="1">1.00</td><td rowspan="1" colspan="1">0.75–1.33</td><td rowspan="1" colspan="1">0.98</td><td rowspan="1" colspan="1">1.03</td><td rowspan="1" colspan="1">0.73–1.43</td><td rowspan="1" colspan="1">0.88</td><td rowspan="1" colspan="1">0.81</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3853</td><td rowspan="1" colspan="1">1058 | 785</td><td rowspan="1" colspan="1">1.00</td><td rowspan="1" colspan="1">0.80–1.26</td><td rowspan="1" colspan="1">0.98</td><td rowspan="1" colspan="1">0.87</td><td rowspan="1" colspan="1">0.66–1.16</td><td rowspan="1" colspan="1">0.34</td><td rowspan="1" colspan="1">0.27</td></tr></tbody></table><table-wrap-foot><fn id="TN3"><p><sup>a</sup>Stratum-specific ORs estimated using polytomous logistic regression.</p></fn><fn id="TN4"><p><sup>b</sup>Stratum-specific <italic>P</italic>-values computed using Wald tests.</p></fn><fn id="TN5"><p><sup>c</sup><italic>P</italic>-value for heterogeneity in effect estimates between strata calculated using case-only logistic regression.</p></fn></table-wrap-foot></table-wrap><table-wrap id="DDV035TB3" position="float"><label>Table 3.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with risk of breast cancer in European women stratified by combined ER/PR status</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Controls</th><th align="left" rowspan="1" colspan="1">Cases</th><th align="left" rowspan="1" colspan="1">ER/PR</th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1"><italic>P</italic><sub>het</sub><sup>c</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1">38 144</td><td rowspan="1" colspan="1">17 132</td><td rowspan="1" colspan="1">ER+/PR+</td><td rowspan="1" colspan="1">1.17</td><td rowspan="1" colspan="1">1.11–1.24</td><td rowspan="1" colspan="1">4.76 × 10<sup>−09</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3380</td><td rowspan="1" colspan="1">ER+/PR−</td><td rowspan="1" colspan="1">1.06</td><td rowspan="1" colspan="1">0.96–1.18</td><td rowspan="1" colspan="1">0.27</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">714</td><td rowspan="1" colspan="1">ER−/PR+</td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">0.90–1.38</td><td rowspan="1" colspan="1">0.30</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4436</td><td rowspan="1" colspan="1">ER−/PR−</td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">0.98–1.18</td><td rowspan="1" colspan="1">0.12</td><td rowspan="1" colspan="1">0.03</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1">38 143</td><td rowspan="1" colspan="1">17 132</td><td rowspan="1" colspan="1">ER+/PR+</td><td rowspan="1" colspan="1">1.13</td><td rowspan="1" colspan="1">1.09–1.16</td><td rowspan="1" colspan="1">6.38 × 10<sup>−08</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3380</td><td rowspan="1" colspan="1">ER+/PR−</td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">1.01–1.15</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">714</td><td rowspan="1" colspan="1">ER−/PR+</td><td rowspan="1" colspan="1">1.00</td><td rowspan="1" colspan="1">0.87–1.15</td><td rowspan="1" colspan="1">0.97</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4438</td><td rowspan="1" colspan="1">ER−/PR−</td><td rowspan="1" colspan="1">1.05</td><td rowspan="1" colspan="1">0.99–1.11</td><td rowspan="1" colspan="1">0.12</td><td rowspan="1" colspan="1">0.01</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1">38 144</td><td rowspan="1" colspan="1">17 128</td><td rowspan="1" colspan="1">ER+/PR+</td><td rowspan="1" colspan="1">0.87</td><td rowspan="1" colspan="1">0.84–0.89</td><td rowspan="1" colspan="1">1.33 × 10<sup>−24</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3380</td><td rowspan="1" colspan="1">ER+/PR−</td><td rowspan="1" colspan="1">0.90</td><td rowspan="1" colspan="1">0.86–0.95</td><td rowspan="1" colspan="1">1.20 × 10<sup>−04</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">714</td><td rowspan="1" colspan="1">ER−/PR+</td><td rowspan="1" colspan="1">0.89</td><td rowspan="1" colspan="1">0.80–1.00</td><td rowspan="1" colspan="1">0.04</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4436</td><td rowspan="1" colspan="1">ER−/PR−</td><td rowspan="1" colspan="1">0.98</td><td rowspan="1" colspan="1">0.94–1.03</td><td rowspan="1" colspan="1">0.47</td><td rowspan="1" colspan="1">4.01 × 10<sup>−06</sup></td></tr></tbody></table><table-wrap-foot><fn id="TN6"><p><sup>a</sup>Stratum-specific ORs estimated using separate logistic regression models comparing cases from each ER/PR combination with all controls.</p></fn><fn id="TN7"><p><sup>b</sup>Stratum-specific <italic>P</italic>-values computed using Wald tests.</p></fn><fn id="TN8"><p><sup>c</sup><italic>P</italic>-value from χ<sup>2</sup>-test of heterogeneity of odds ratios.</p></fn></table-wrap-foot></table-wrap></p><p>There was little evidence for heterogeneity in the effects conferred by SNPs rs10816625, rs13294895 and rs676256 according to human epidermal growth factor receptor 2 (HER2) expression (Table <xref ref-type="table" rid="DDV035TB2">2</xref>). We also observed no evidence of heterogeneity in effects conferred by rs10816625 according to either tumour ER or PR status in subjects with Asian ancestry (Table <xref ref-type="table" rid="DDV035TB2">2</xref>).</p><p>Because all three SNPs reported in our fine-mapping analysis of Europeans were primarily associated with ER-positive, but not ER-negative tumours, we restricted further stratified analyses of additional breast cancer risk factors to cases with ER-positive disease. However, the results from analyses of all breast cancers combined and from ER-negative breast cancers are presented in <ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Tables S4–S7</ext-link>. In Europeans, but not Asians, the effect of rs10816625 was stronger in cases with node-negative (OR = 1.19 [1.12–1.25], <italic>P</italic> = 4.55 × 10<sup>−09</sup>; Table <xref ref-type="table" rid="DDV035TB4">4</xref>) than in those with node-positive disease (OR = 1.07 [0.99–1.14], <italic>P</italic> = 0.07, <italic>P</italic><sub>het</sub> = 5.98 × 10<sup>−03</sup>; Table <xref ref-type="table" rid="DDV035TB4">4</xref>). There was no significant evidence of interaction according to tumour morphology (Table <xref ref-type="table" rid="DDV035TB5">5</xref>). We observed evidence of a linearly increasing trend in the OR by grade for rs10816625 in Asians only (<italic>P</italic><sub>trend</sub> = 4.91 × 10<sup>−04</sup>; Table <xref ref-type="table" rid="DDV035TB6">6</xref>). We previously reported a trend in per-allele OR for rs865686 with increasing age at diagnosis in ER-positive breast cancer, with a stronger association at younger ages (<xref rid="DDV035C21" ref-type="bibr">21</xref>). Here we report that the same was true for rs676256 in women of European ancestry (<italic>P</italic><sub>trend</sub> = 0.02; Table <xref ref-type="table" rid="DDV035TB7">7</xref>); we saw no compelling evidence of a similar age interaction for rs10816625 or rs13294895 (Table <xref ref-type="table" rid="DDV035TB7">7</xref>). Because the 9q31.2 breast cancer locus was initially discovered in a study enriched for bilateral and familial cases we estimated ORs for each SNP in sporadic, familial and bilateral cases (<ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S8</ext-link>). There were no statistically significant differences in ORs between sporadic and either bilateral or familial cases.
<table-wrap id="DDV035TB4" position="float"><label>Table 4.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with risk of ER-positive breast cancer stratified by lymph node status</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Population</th><th align="left" rowspan="1" colspan="1">Controls</th><th align="left" rowspan="1" colspan="1">Cases</th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1"><italic>P</italic><sub>het</sub><sup>c</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Caucasian</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" align="center" rowspan="1">Node-negative tumours</td><td colspan="3" align="center" rowspan="1">Node-positive tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">40 313</td><td rowspan="1" colspan="1">13 093 | 8235</td><td rowspan="1" colspan="1">1.19</td><td rowspan="1" colspan="1">1.12–1.25</td><td rowspan="1" colspan="1">4.55 × 10<sup>−09</sup></td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">0.99–1.14</td><td rowspan="1" colspan="1">0.07</td><td rowspan="1" colspan="1">5.98 × 10<sup>−03</sup></td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">40 313</td><td rowspan="1" colspan="1">13 093 | 8235</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">1.06–1.15</td><td rowspan="1" colspan="1">1.36 × 10<sup>−07</sup></td><td rowspan="1" colspan="1">1.13</td><td rowspan="1" colspan="1">1.08–1.18</td><td rowspan="1" colspan="1">7.90 × 10<sup>−08</sup></td><td rowspan="1" colspan="1">0.43</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">40 313</td><td rowspan="1" colspan="1">13 090 | 8234</td><td rowspan="1" colspan="1">0.86</td><td rowspan="1" colspan="1">0.84–0.89</td><td rowspan="1" colspan="1">5.42 × 10<sup>−22</sup></td><td rowspan="1" colspan="1">0.90</td><td rowspan="1" colspan="1">0.87–0.93</td><td rowspan="1" colspan="1">1.17 × 10<sup>−08</sup></td><td rowspan="1" colspan="1">0.04</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Asian</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" align="center" rowspan="1">Node-negative tumours</td><td colspan="3" align="center" rowspan="1">Node-positive tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4741</td><td rowspan="1" colspan="1">1084 | 740</td><td rowspan="1" colspan="1">1.13</td><td rowspan="1" colspan="1">1.02–1.25</td><td rowspan="1" colspan="1">0.02</td><td rowspan="1" colspan="1">1.11</td><td rowspan="1" colspan="1">0.98–1.24</td><td rowspan="1" colspan="1">0.03</td><td rowspan="1" colspan="1">0.77</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4742</td><td rowspan="1" colspan="1">1083 | 740</td><td rowspan="1" colspan="1">1.16</td><td rowspan="1" colspan="1">0.88–1.53</td><td rowspan="1" colspan="1">0.29</td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">0.78–1.49</td><td rowspan="1" colspan="1">0.66</td><td rowspan="1" colspan="1">0.72</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4742</td><td rowspan="1" colspan="1">1084 | 740</td><td rowspan="1" colspan="1">1.02</td><td rowspan="1" colspan="1">0.81–1.29</td><td rowspan="1" colspan="1">0.85</td><td rowspan="1" colspan="1">1.01</td><td rowspan="1" colspan="1">0.77–1.31</td><td rowspan="1" colspan="1">0.97</td><td rowspan="1" colspan="1">0.94</td></tr></tbody></table><table-wrap-foot><fn id="TN9"><p><sup>a</sup>Stratum-specific ORs estimated using polytomous logistic regression.</p></fn><fn id="TN10"><p><sup>b</sup>Stratum-specific <italic>P</italic>-values computed using Wald tests.</p></fn><fn id="TN11"><p><sup>c</sup><italic>P</italic>-value for heterogeneity in effect estimates between strata calculated using case-only logistic regression.</p></fn></table-wrap-foot></table-wrap><table-wrap id="DDV035TB5" position="float"><label>Table 5.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with ER-positive breast cancer stratified by morphology</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Population</th><th align="left" rowspan="1" colspan="1">Controls</th><th align="left" rowspan="1" colspan="1">Cases</th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1">OR<sup>a</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>b</sup></th><th align="left" rowspan="1" colspan="1"><italic>P</italic><sub>het</sub><sup>c</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Caucasian</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" align="center" rowspan="1">Ductal tumours</td><td colspan="3" align="center" rowspan="1">Lobular tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">34 151</td><td rowspan="1" colspan="1">15 007 | 3199</td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.05–1.18</td><td rowspan="1" colspan="1">1.25 × 10<sup>−04</sup></td><td rowspan="1" colspan="1">1.17</td><td rowspan="1" colspan="1">1.06–1.30</td><td rowspan="1" colspan="1">1.91 × 10<sup>−03</sup></td><td rowspan="1" colspan="1">0.35</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">34 149</td><td rowspan="1" colspan="1">15 007 | 3199</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">1.06–1.14</td><td rowspan="1" colspan="1">5.51 × 10<sup>−07</sup></td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.05–1.20</td><td rowspan="1" colspan="1">5.43 × 10<sup>−04</sup></td><td rowspan="1" colspan="1">0.42</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">34 150</td><td rowspan="1" colspan="1">15 004 | 3199</td><td rowspan="1" colspan="1">0.88</td><td rowspan="1" colspan="1">0.85–0.90</td><td rowspan="1" colspan="1">1.16 × 10<sup>−18</sup></td><td rowspan="1" colspan="1">0.84</td><td rowspan="1" colspan="1">0.80–0.89</td><td rowspan="1" colspan="1">5.64 × 10<sup>−10</sup></td><td rowspan="1" colspan="1">0.17</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Asian</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td colspan="3" align="center" rowspan="1">Ductal tumours</td><td colspan="3" align="center" rowspan="1">Lobular tumours</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3852</td><td rowspan="1" colspan="1">1800 | 85</td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.03–1.22</td><td rowspan="1" colspan="1">8.50 × 10<sup>−03</sup></td><td rowspan="1" colspan="1">1.29</td><td rowspan="1" colspan="1">0.94–1.77</td><td rowspan="1" colspan="1">0.11</td><td rowspan="1" colspan="1">0.32</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3853</td><td rowspan="1" colspan="1">1799 | 85</td><td rowspan="1" colspan="1">1.16</td><td rowspan="1" colspan="1">0.92–1.46</td><td rowspan="1" colspan="1">0.22</td><td rowspan="1" colspan="1">1.16</td><td rowspan="1" colspan="1">0.47–2.87</td><td rowspan="1" colspan="1">0.74</td><td rowspan="1" colspan="1">0.96</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3853</td><td rowspan="1" colspan="1">1800 | 85</td><td rowspan="1" colspan="1">0.91</td><td rowspan="1" colspan="1">0.74–1.12</td><td rowspan="1" colspan="1">0.38</td><td rowspan="1" colspan="1">1.58</td><td rowspan="1" colspan="1">0.84–2.96</td><td rowspan="1" colspan="1">0.16</td><td rowspan="1" colspan="1">0.13</td></tr></tbody></table><table-wrap-foot><fn id="TN12"><p><sup>a</sup>Stratum-specific ORs estimated using polytomous logistic regression.</p></fn><fn id="TN13"><p><sup>b</sup>Stratum-specific <italic>P</italic>-values computed using Wald tests.</p></fn><fn id="TN14"><p><sup>c</sup><italic>P</italic>-value for heterogeneity in effect estimates between strata calculated using case-only logistic regression.</p></fn></table-wrap-foot></table-wrap><table-wrap id="DDV035TB6" position="float"><label>Table 6.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with ER-positive breast cancer stratified by tumour grade</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Population</th><th align="left" rowspan="1" colspan="1">Controls</th><th align="left" rowspan="1" colspan="1">Cases<sup>a</sup></th><th align="left" rowspan="1" colspan="1">Grade</th><th align="left" rowspan="1" colspan="1">OR<sup>b</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>c</sup></th><th align="left" rowspan="1" colspan="1"><italic>P</italic><sub>trend</sub><sup>d</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1">Caucasian</td><td rowspan="1" colspan="1">39 762</td><td rowspan="1" colspan="1">5233</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1.16</td><td rowspan="1" colspan="1">1.07–1.26</td><td rowspan="1" colspan="1">4.26 × 10<sup>−04</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">11 432</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">1.14</td><td rowspan="1" colspan="1">1.07–1.16</td><td rowspan="1" colspan="1">1.91 × 10<sup>−05</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4 655</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">1.09</td><td rowspan="1" colspan="1">1.00–1.19</td><td rowspan="1" colspan="1">0.05</td><td rowspan="1" colspan="1">0.26</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">39 763</td><td rowspan="1" colspan="1">5233</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1.08</td><td rowspan="1" colspan="1">1.02–1.14</td><td rowspan="1" colspan="1">0.005</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">11 432</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">1.11</td><td rowspan="1" colspan="1">1.07–1.16</td><td rowspan="1" colspan="1">4.35 × 10<sup>−08</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4655</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">1.04–1.17</td><td rowspan="1" colspan="1">5.33 × 10<sup>−04</sup></td><td rowspan="1" colspan="1">0.60</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">39 763</td><td rowspan="1" colspan="1">5232</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">0.88</td><td rowspan="1" colspan="1">0.84–0.92</td><td rowspan="1" colspan="1">2.27 × 10<sup>−09</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">11 429</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">0.87</td><td rowspan="1" colspan="1">0.84–0.89</td><td rowspan="1" colspan="1">1.13 × 10<sup>−19</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4655</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">0.88</td><td rowspan="1" colspan="1">0.84–0.92</td><td rowspan="1" colspan="1">6.40 × 10<sup>−08</sup></td><td rowspan="1" colspan="1">0.96</td></tr><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1">Asian</td><td rowspan="1" colspan="1">4488</td><td rowspan="1" colspan="1">331</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1.02</td><td rowspan="1" colspan="1">0.86–1.20</td><td rowspan="1" colspan="1">0.85</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">961</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">0.98–1.22</td><td rowspan="1" colspan="1">0.09</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">427</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">1.42</td><td rowspan="1" colspan="1">1.22–1.65</td><td rowspan="1" colspan="1">4.88 × 10<sup>−06</sup></td><td rowspan="1" colspan="1">4.91 × 10<sup>−04</sup></td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4489</td><td rowspan="1" colspan="1">331</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">0.85</td><td rowspan="1" colspan="1">0.51–1.43</td><td rowspan="1" colspan="1">0.54</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">961</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">1.17</td><td rowspan="1" colspan="1">0.86–1.57</td><td rowspan="1" colspan="1">0.32</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">427</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">1.25</td><td rowspan="1" colspan="1">0.84–1.87</td><td rowspan="1" colspan="1">0.27</td><td rowspan="1" colspan="1">0.46</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">4489</td><td rowspan="1" colspan="1">331</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">0.75–1.53</td><td rowspan="1" colspan="1">0.72</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">961</td><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">1.04</td><td rowspan="1" colspan="1">0.81–1.33</td><td rowspan="1" colspan="1">0.75</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">427</td><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">0.68</td><td rowspan="1" colspan="1">0.46–1.02</td><td rowspan="1" colspan="1">0.06</td><td rowspan="1" colspan="1">0.06</td></tr></tbody></table><table-wrap-foot><fn id="TN15"><p><sup>a</sup>Maximum total number of cases for each stratum.</p></fn><fn id="TN16"><p><sup>b</sup>Stratum-specific ORs estimated using polytomous logistic regression.</p></fn><fn id="TN17"><p><sup>c</sup>Stratum-specific <italic>P</italic>-values computed using Wald tests.</p></fn><fn id="TN18"><p><sup>d</sup><italic>P</italic>-value for linear trend in effect estimates across strata calculated using case-only logistic regression.</p></fn></table-wrap-foot></table-wrap><table-wrap id="DDV035TB7" position="float"><label>Table 7.</label><caption><p>Association of rs10816625, rs13294895 and rs676256 with ER-positive breast cancer in Europeans, stratified by age at diagnosis</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Locus</th><th align="left" rowspan="1" colspan="1">Controls</th><th align="left" rowspan="1" colspan="1">Cases<sup>a</sup></th><th align="left" rowspan="1" colspan="1">Age Group</th><th align="left" rowspan="1" colspan="1">OR<sup>b</sup></th><th align="left" rowspan="1" colspan="1">95% CI</th><th align="left" rowspan="1" colspan="1"><italic>P</italic>-value<sup>c</sup></th><th align="left" rowspan="1" colspan="1"><italic>P</italic><sub>trend</sub><sup>d</sup></th></tr></thead><tbody><tr><td rowspan="1" colspan="1">rs10816625</td><td rowspan="1" colspan="1">30 239</td><td rowspan="1" colspan="1">988</td><td rowspan="1" colspan="1"><40</td><td rowspan="1" colspan="1">1.18</td><td rowspan="1" colspan="1">0.99–1.41</td><td rowspan="1" colspan="1">0.06</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3858</td><td rowspan="1" colspan="1">40–49</td><td rowspan="1" colspan="1">1.20</td><td rowspan="1" colspan="1">1.09–1.32</td><td rowspan="1" colspan="1">1.39 × 10<sup>−4</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6865</td><td rowspan="1" colspan="1">50–59</td><td rowspan="1" colspan="1">1.14</td><td rowspan="1" colspan="1">1.06–1.23</td><td rowspan="1" colspan="1">6.93 × 10<sup>−4</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6173</td><td rowspan="1" colspan="1">60–69</td><td rowspan="1" colspan="1">1.13</td><td rowspan="1" colspan="1">1.04–1.22</td><td rowspan="1" colspan="1">0.003</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">2679</td><td rowspan="1" colspan="1">≥70</td><td rowspan="1" colspan="1">1.10</td><td rowspan="1" colspan="1">0.99–1.24</td><td rowspan="1" colspan="1">0.08</td><td rowspan="1" colspan="1">0.25</td></tr><tr><td rowspan="1" colspan="1">rs13294895</td><td rowspan="1" colspan="1">30 239</td><td rowspan="1" colspan="1">988</td><td rowspan="1" colspan="1"><40</td><td rowspan="1" colspan="1">1.07</td><td rowspan="1" colspan="1">0.95–1.20</td><td rowspan="1" colspan="1">0.26</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3858</td><td rowspan="1" colspan="1">40–49</td><td rowspan="1" colspan="1">1.15</td><td rowspan="1" colspan="1">1.08–1.22</td><td rowspan="1" colspan="1">7.84 × 10<sup>−06</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6865</td><td rowspan="1" colspan="1">50–59</td><td rowspan="1" colspan="1">1.12</td><td rowspan="1" colspan="1">1.07–1.18</td><td rowspan="1" colspan="1">2.42 × 10<sup>−06</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6173</td><td rowspan="1" colspan="1">60–69</td><td rowspan="1" colspan="1">1.11</td><td rowspan="1" colspan="1">1.05–1.16</td><td rowspan="1" colspan="1">6.70 × 10<sup>−05</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">2679</td><td rowspan="1" colspan="1">≥70</td><td rowspan="1" colspan="1">1.04</td><td rowspan="1" colspan="1">0.97–1.12</td><td rowspan="1" colspan="1">0.25</td><td rowspan="1" colspan="1">0.13</td></tr><tr><td rowspan="1" colspan="1">rs676256</td><td rowspan="1" colspan="1">30 240</td><td rowspan="1" colspan="1">987</td><td rowspan="1" colspan="1"><40</td><td rowspan="1" colspan="1">0.89</td><td rowspan="1" colspan="1">0.81–0.98</td><td rowspan="1" colspan="1">0.02</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">3858</td><td rowspan="1" colspan="1">40–49</td><td rowspan="1" colspan="1">0.82</td><td rowspan="1" colspan="1">0.78–0.86</td><td rowspan="1" colspan="1">5.13 × 10<sup>−14</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6864</td><td rowspan="1" colspan="1">50–59</td><td rowspan="1" colspan="1">0.86</td><td rowspan="1" colspan="1">0.83–0.90</td><td rowspan="1" colspan="1">1.03 × 10<sup>−13</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">6171</td><td rowspan="1" colspan="1">60–69</td><td rowspan="1" colspan="1">0.89</td><td rowspan="1" colspan="1">0.86–0.93</td><td rowspan="1" colspan="1">7.56 × 10<sup>−08</sup></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">2679</td><td rowspan="1" colspan="1">≥70</td><td rowspan="1" colspan="1">0.92</td><td rowspan="1" colspan="1">0.87–0.98</td><td rowspan="1" colspan="1">0.006</td><td rowspan="1" colspan="1">0.02</td></tr></tbody></table><table-wrap-foot><fn id="TN19"><p><sup>a</sup>Maximum total number of cases for each stratum.</p></fn><fn id="TN20"><p><sup>b</sup>Stratum-specific ORs estimated using polytomous logistic regression.</p></fn><fn id="TN21"><p><sup>c</sup>Stratum-specific <italic>P</italic>-values computed using Wald tests.</p></fn><fn id="TN22"><p><sup>d</sup><italic>P</italic>-value for linear trend in effect estimates across strata calculated using case-only logistic regression.</p></fn></table-wrap-foot></table-wrap></p><p>In an effort to identify putative causal variants underlying each of the three associations, we performed a bioinformatic analysis. We used data from the ENCODE project (<xref rid="DDV035C24" ref-type="bibr">24</xref>) and elsewhere (<xref rid="DDV035C25" ref-type="bibr">25</xref>) to explore the co-localisation of the association signals with features indicative of functional genomic elements in breast cancer models, including evidence of transcription factor binding, DNase hypersensitivity and relevant histone modification marks. Both SNPs rs10816625 and rs13294895 localise to a region of putative regulatory significance in MCF7 cells, demarcated by histone H3 lysine 27 acetylation (H3K27ac) and histone H3 lysine 4 mono-methylation (H3K4me1), both of which are characteristic features of active enhancers (Fig. <xref ref-type="fig" rid="DDV035F2">2</xref>A) (<xref rid="DDV035C26" ref-type="bibr">26</xref>,<xref rid="DDV035C27" ref-type="bibr">27</xref>). There was less evidence for either histone modification mark in human mammary epithelial cells (HMEC; not shown). Both SNPs are located directly under the binding sites for a number of breast cancer-relevant transcription factors, including forkhead box M1 (FOXM1) and GATA binding protein 3 (GATA3; Fig. <xref ref-type="fig" rid="DDV035F2">2</xref>A) (<xref rid="DDV035C28" ref-type="bibr">28</xref>,<xref rid="DDV035C29" ref-type="bibr">29</xref>).
<fig id="DDV035F2" position="float"><label>Figure 2.</label><caption><p>Plots of genomic annotations with putative functional significance at the 9q31.2 fine-mapping region. (<bold>A</bold>) Publically available histone modification, DNase hypersensitivity and transcription factor binding data from MCF7 cells were mapped on to the breast cancer associated regions identified by fine-mapping. For SNPs rs10826625 and rs13294895, the iCHAVs were defined as SNPs having <italic>r</italic><sup>2</sup> ≥ 0.8 with either SNP; for rs676256 it was defined as all SNPs with <italic>r</italic><sup>2</sup> ≥ 0.8 and likelihood ratios >1:100 relative to rs676256. There were no other SNPs in the iCHAVs for rs10816625 and rs13294895. The rs676256 iCHAV comprised 28 SNPs. SNPs whose identifiers are shown in red type were of putative functional significance (see Materials and Methods). Where the lead SNP was not deemed to be of putative functional significance, it is indicated in green, as is the index 9q31.2 SNP, rs865686. (<bold>B</bold>) Regional binding profiles for ER-α in MCF7 cells shown plotted across the fine-mapping region using data from (<xref rid="DDV035C31" ref-type="bibr">31</xref>). The locations of the lead SNPs are indicated with yellow diamonds. (<bold>C</bold>) Regional binding profiles for FOXA1 in MCF7 cells shown plotted across the fine-mapping region using data from (<xref rid="DDV035C31" ref-type="bibr">31</xref>). The locations of the lead SNPs are indicated with yellow diamonds.</p></caption><graphic xlink:href="ddv03502"></graphic></fig></p><p>To reduce the number of candidate functional polymorphisms for the rs676256 iCHAV, we applied a heuristic scoring system to prioritise variants that localise to regions with cistromic and epigenetic activity (<xref rid="DDV035C30" ref-type="bibr">30</xref>). We identified three variants in this iCHAV that co-localise with potentially relevant genomic features (Fig. <xref ref-type="fig" rid="DDV035F2">2</xref>A). Specifically, all three variants lie in regions of open chromatin in MCF7 cells (Fig. <xref ref-type="fig" rid="DDV035F2">2</xref>A). SNPs rs662694 (110 887 996 bp; OR = 0.88 [0.87–0.90]; <italic>P</italic> = 5.64 × 10<sup>−25</sup>) and rs471467 (110 888 113 bp; OR = 0.88 [0.87–0.90]; <italic>P</italic> = 3.30 × 10<sup>−25</sup>) localise to a CTCF binding site, which suggests insulator activity, while insertion–deletion (indel) polymorphism rs5899787 (110 893 551–2 bp; OR = 0.88 [0.87–0.90]; <italic>P</italic> = 1.67 × 10<sup>−24</sup>) lies in a region with features of a poised enhancer, namely enrichment of histone H3 lysine 27 trimethylation (H3K27me3) and has evidence of FOXM1 and GATA3 binding in MCF7 cells (Fig. <xref ref-type="fig" rid="DDV035F2">2</xref>A).</p><p>Estrogen receptor-α (ER-α) and forkhead box A1 (FOXA1) are key drivers of ER-positive breast cancer. Because there are currently limited ENCODE data on either of these factors, we explored their binding at the 9q31.2 susceptibility locus in MCF7 cells using data from Hurtado <italic>et al.</italic> (<xref rid="DDV035C31" ref-type="bibr">31</xref>). We found that the three lead SNPs localise to binding sites for both transcription factors (Fig. <xref ref-type="fig" rid="DDV035F2">2</xref>B and C). SNPs rs10816625 and rs13294895 map directly under ER-α and FOXA1 binding peaks which co-localise to the putative active enhancer described above. rs5899787, from the rs676256 iCHAV, also maps directly under an ER-α and FOXA1 binding peak; none of the other SNPs in the rs676256 iCHAV map to this, or any other ER-α and FOXA1 peaks.</p><p>A recent integrative analysis of data from The Cancer Genome Atlas suggested that the original 9q31.2 risk locus influences transcript levels of <italic>KLF4</italic> (<xref rid="DDV035C32" ref-type="bibr">32</xref>). We investigated, using chromosome conformation capture (3C) in <italic>Hin</italic>dIII digested MCF7 (Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>A) and SUM44 (Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>B) 3C libraries, whether the locus containing SNPs rs10816625 and rs13294895 also interacts with <italic>KLF4</italic> through long-range chromatin interaction. We detected elevated interaction frequencies between <italic>Hin</italic>dIII fragments containing SNPs rs10816625 and rs13294895 and those containing <italic>KLF4</italic>; interactions with <italic>Hin</italic>dIII fragments either side of <italic>KLF4</italic> were lower in comparison. Moreover no interaction was detected between the fragment containing SNPs rs10816625 and rs13294895 with <italic>RAD23B</italic>.
<fig id="DDV035F3" position="float"><label>Figure 3.</label><caption><p>Chromatin conformation capture and reporter gene analysis of SNPs rs10816625 and rs13294895. (<bold>A</bold>) Chromatin interaction data from <italic>Hin</italic>dIII 3C libraries generated using MCF7 cells that indicates interactions between a fragment containing rs10816625 and rs13294895 (dashed line) and fragments surrounding <italic>KLF4</italic>. Results from three replicate libraries are plotted; each quantitative PCR reaction was performed in triplicate. Error bars represent standard mean errors. (<bold>B</bold>) Chromatin interaction data from <italic>Hin</italic>dIII 3C libraries generated using SUM44 cells. (<bold>C</bold>) Dual luciferase assays for reporter constructs containing the common alleles of both rs10816625 and rs13294895 (pGL4minP-AB), risk allele of rs10816625 (pGL4minP-aB), risk allele of rs13294895 (pGL4minP-Ab) and risk alleles of both SNPs (pGL4minP-ab) transiently transfected into MCF7 cells. Ratios were normalised to a minimal promoter construct (pGL4minP). Each transfection was repeated five times and constructs were generated in both forward and reverse orientations. (<bold>D</bold>) Dual luciferase assays for reporter constructs containing the common alleles of both rs10816625 and rs13294895 (pGL4minP-AB), risk allele of rs10816625 (pGL4minP-aB), risk allele of rs13294895 (pGL4minP-Ab) and risk alleles of both SNPs (pGL4minP-ab) transiently transfected into T47D cells.</p></caption><graphic xlink:href="ddv03503"></graphic></fig></p><p>To determine whether either locus had enhancer activity we performed a series of dual luciferase assays using a minimal promoter vector, pGL4minP. To explore the rs10816625/rs13294895 locus we inserted a 1 kb fragment containing the common alleles of both variants, plus flanking DNA, into pGL4minP (pGL4minP-AB). We observed an increased level of activity of the minimal promoter in the pGL4minP-AB construct relative to pGL4minP in both MCF7 (8.2-fold increase; <italic>P</italic> = 6.12 × 10<sup>−05</sup>; Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>C) and T47D cells (3.1-fold increase; <italic>P</italic> = 6.66 × 10<sup>−04</sup>; Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>D). To determine whether the risk alleles of rs10816625 and rs13294895 disrupted this enhancer activity we generated three additional constructs, carrying a single risk allele of either rs10816625 (pGL4minP-aB) or rs13294895 (pGL4minP-Ab), or carrying risk alleles of both SNPs (pGL4minP-ab). We observed significant evidence for a difference in the means of the dual luciferase ratios of these constructs in MCF7 and T47D cells (<italic>P</italic> < 7 × 10<sup>−04</sup>; Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>C and D). In T47D cells we found a statistically significant difference between pGL4minP-AB and either pGL4minP-aB (<italic>P</italic> = 5.45 × 10<sup>−03</sup>), pGL4minP-Ab (<italic>P</italic> = 0.04) or pGL4minP-ab (<italic>P</italic> = 4.97 × 10<sup>−04</sup>; Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>D). In MCF7 cells there was a statistically significant difference between pGL4minP-AB and pGL4minP-aB (<italic>P</italic> = 6.62 × 10<sup>−05</sup>), but not pGL4minP-Ab (Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>C). There was no significant difference between the construct containing both risk alleles and constructs containing one risk allele in T47D cells (Fig. <xref ref-type="fig" rid="DDV035F3">3</xref>D). We performed a similar series of analyses to explore the putative poised enhancer centred on SNP rs5899787. Relative to pGL4minP, we observed a reduction in reporter gene expression but saw no evidence to support an allele-specific effect (data not shown).</p></sec><sec sec-type="discussion" id="s3"><title>Discussion</title><p>In a combined analysis of data from 50 case–control studies comprising more than 100 000 women, we have refined the localisation of the breast cancer association signal on chromosome 9q31.2 to a set of 28 highly correlated variants in a 14.5 kb region in which SNP rs676256 was the most strongly associated variant. Furthermore we have demonstrated the presence of two novel independent susceptibility alleles at 9q31.2, SNPs rs10816625 and rs13294895, both of which are strong candidates to be causal variants. Breast cancer is a heterogeneous disease comprising multiple subtypes that can be classified according to histological, immunophenotypic and molecular characteristics. Although the majority of known breast cancer susceptibility loci are preferentially associated with ER-positive tumours (<xref rid="DDV035C33" ref-type="bibr">33</xref>), a number of recent subtype-specific studies have detected genetic associations unique to ER-negative tumours, suggesting distinct underlying aetiologies for each subtype (<xref rid="DDV035C17" ref-type="bibr">17</xref>,<xref rid="DDV035C34" ref-type="bibr">34</xref>,<xref rid="DDV035C35" ref-type="bibr">35</xref>). The index 9q31.2 breast cancer susceptibility association, demarcated by SNP rs865686 (<xref rid="DDV035C7" ref-type="bibr">7</xref>), was largely restricted to ER-positive breast cancer (<xref rid="DDV035C21" ref-type="bibr">21</xref>) and this was confirmed for rs676256 in the European samples analysed in this study. SNPs rs10816625 and rs13294895 were also associated with ER-positive, but not ER-negative, breast cancer in Europeans, albeit with more modest statistical evidence of heterogeneity than for rs672656.</p><p>The majority of susceptibility loci for breast and other cancers have been detected using studies of predominantly European ancestry. However, confirmation of associations in populations with different ethnicity from those used for discovery can add weight to their validity (<xref rid="DDV035C36" ref-type="bibr">36</xref>). Approximately 10% of the samples genotyped in our fine-mapping study were from subjects of Asian ancestry. In Asians, rs10816625 had a higher MAF than in Europeans and was the only SNP that was significantly associated with breast cancer risk; the OR was similar to that in Europeans. Neither rs676256 nor rs13294895 were significantly associated with risk in Asians, but the MAFs were much smaller than in Europeans and the ORs did not differ by ethnicity. SNP rs10816625 resides on a strong hotspot of recombination in Europeans and exhibits low pairwise correlation with all but two other SNPs, each of which has a <italic>P</italic>-value for association with breast cancer several orders of magnitude larger than that of rs10816625. These observations provide evidence that rs10816625 was causally associated with breast cancer.</p><p>The third breast cancer susceptibility SNP that we detected, rs13294895, localises to within ∼100 bp of rs10816625. Analysis of computationally phased haplotypes indicates that their risk alleles rarely occur together, consistent with having arisen independently on the same ancestral haplotype with little subsequent recombination.</p><p>We used bioinformatic annotation of the regions demarcated by SNPs rs10816625, rs13294895 and rs676256 to identify a set of variants that had putative regulatory potential and, as such, were candidates to be the causal alleles underlying the observed associations. SNPs rs10816625 and rs13294895 localise to a region with a histone modification signature that suggests it is an active enhancer in MCF7 cells. We also saw evidence that supports binding of ER-α, FOXA1 and GATA3 at this locus, directly over the sites of rs10816625 and rs13294895. ER-α is an established driver of luminal breast cancer and FOXA1 is a pioneer factor that physically interacts with compacted chromatin, facilitating binding of ER-α, and is necessary for ER-α mediated transcription (<xref rid="DDV035C31" ref-type="bibr">31</xref>,<xref rid="DDV035C37" ref-type="bibr">37</xref>). GATA3 is thought to play a key role in making enhancer elements accessible to ER-α and its expression is highly correlated with both ER-α and FOXA1 in breast tumours (<xref rid="DDV035C38" ref-type="bibr">38</xref>,<xref rid="DDV035C39" ref-type="bibr">39</xref>). Of note, Cowper-Sal·lari <italic>et al</italic> have recently demonstrated that breast cancer susceptibility loci are enriched for ER-α and FOXA1 binding events (<xref rid="DDV035C40" ref-type="bibr">40</xref>). Our <italic>in vitro</italic> data support the hypothesis that this locus possesses enhancer activity and indicate that the risk alleles of rs10816625 and rs13294895 can diminish its activity, indicating that these are independent risk susceptibility variants acting through the same mechanism.</p><p>Li <italic>et al.</italic> have recently suggested the original 9q31.2 breast cancer susceptibility locus acts via regulation of the transcription factor KLF4 (<xref rid="DDV035C32" ref-type="bibr">32</xref>). In their article these authors identified <italic>KLF4</italic> as the target of the 9q31.2 locus on the basis of a trans-eQTL analysis in which they first identified the set of eQTL genes associated with rs471467 (a perfect proxy for rs865686) and then looked for enrichment of transcription factor binding sites within ENCODE defined enhancer elements of these genes. We have demonstrated an excess of long-range chromatin interactions between the rs10816625/rs13294895 region and the <italic>KLF4</italic> gene locus. Our results and those of Li <italic>et al.</italic> suggest therefore that <italic>KLF4</italic> is the target of multiple 9q31.2 breast cancer susceptibility SNPs. In contrast to recent eQTL analysis by Li and colleagues implicating <italic>RAD23B</italic> as the target of the prostate cancer susceptibility SNP rs817826, we found no evidence that these breast cancer SNPs interacted with <italic>RAD23B</italic> (<xref rid="DDV035C41" ref-type="bibr">41</xref>). KLF4 has both oncogenic and tumour suppressive roles depending on the tissue in which it is expressed (<xref rid="DDV035C42" ref-type="bibr">42</xref>). It is thought to be expressed at low levels in normal breast epithelium, but is overexpressed in a large proportion of both ductal carcinoma in situ and invasive breast cancer (<xref rid="DDV035C43" ref-type="bibr">43</xref>). Our reporter assays targeting the rs10816625/rs13294895 SNPs suggest that lower levels of expression of KLF4 are associated with increased breast cancer risk.</p><p>In contrast to the rs10816625/rs13294895 locus, refinement of the association signal at the rs676256 locus was complicated by the large number of variants in high LD with the lead SNP. Of the 28 highly correlated variants in this iCHAV, analysis of ENCODE data identified three that fall into two distinct functional regions. SNPs rs662694 and rs471467 localise to a predicted insulator region, defined by CTCF binding and H3K27me3 marks (<xref rid="DDV035C44" ref-type="bibr">44</xref>). SNP rs5899787 was located in a region that shared similar functionally significant features to those of the rs10816625/rs13294895 locus. It localises directly to a second site of strong ER-α and FoxA1 co-localisation and had strong evidence of GATA-3 binding in the ENCODE data. Our data suggested that a construct containing the common allele of rs5899787 suppressed the activity of the minimal promoter in our reporter gene system, but we saw no evidence for an allele-specific effect. Further work will be required to determine the identity and mode of action of the causative variant (or variants) at this locus.</p><p>Including the variants identified in our study, 81 common germline polymorphisms conferring susceptibility to breast cancer have now been identified. Our study, and those of others, demonstrate the power of fine-mapping in large studies both for the detection of novel independent susceptibility SNPs and determining a minimal set of likely causal variants (<xref rid="DDV035C15" ref-type="bibr">15</xref>,<xref rid="DDV035C16" ref-type="bibr">16</xref>).</p></sec><sec sec-type="materials|methods" id="s4"><title>Materials and Methods</title><sec id="s4a"><title>Sample selection</title><p>Samples (<italic>n</italic> = 103 991) were selected from 52 studies participating in BCAC and genotyped as part of the COGS project (<xref rid="DDV035C9" ref-type="bibr">9</xref>). Most contributing studies were either population or hospital-based case–control studies, while some were nested in cohorts or selected for family history, age or tumour characteristics. Full details of contributing studies can be found in <ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S1</ext-link>. Four studies, Demokritos (DEMOKRITOS), Ohio State University (OSU), Städtisches Klinikum Karlsruhe Deutsches Krebsforschungszentrum Study (SKKDKFZS) and the Roswell Park Cancer Institute Study (RPCI) were genotyped as part of the Triple Negative Breast Cancer Case–control Consortium, but are analysed here in their component studies. Analyses were restricted to cases with invasive breast cancer. All analyses reported were stratified according to ancestry of the study participants, categorised as having predominantly European (<italic>n</italic> = 43 160 cases; 42 600 controls), Asian (<italic>n</italic> = 5795 cases; 6624 controls) or African ancestry (<italic>n</italic> = 1046 cases; 932 controls), determined by a principal components analysis of 37 000 uncorrelated SNPs ancestry-informative markers, described elsewhere (<xref rid="DDV035C9" ref-type="bibr">9</xref>). All BCAC studies had local ethical approval.</p></sec><sec id="s4b"><title>Genotyping and quality control</title><p>A total of 447 fine-mapping SNPs were selected to interrogate the 9q31.2 locus. The fine-mapping region was defined as the region that included including all SNPs correlated with the index SNP, rs865686, at <italic>r</italic><sup>2</sup> > 0.1. For genotyping we first selected all SNPs with an Illumina Design Score >0.8 and <italic>r</italic><sup>2</sup> with rs865686 >0.1. We then selected an additional set of SNPs designed to tag all remaining SNPs in the interval at <italic>r</italic><sup>2</sup> > 0.9. Genotyping was performed using a custom-designed International Collaborative Oncology Gene-environment Study (iCOGS) genotyping array (Illumina, San Diego, CA). The iCOGS array comprised assays for 211 155 SNPs, primarily selected for replication analysis of loci putatively associated with breast, ovarian or prostate cancer and for fine-mapping of the known susceptibility loci for these cancers. Full details of the iCOGS array design, sample handling and post-genotyping QC processes are described in-depth elsewhere (<xref rid="DDV035C9" ref-type="bibr">9</xref>). Briefly, samples were excluded from the analytic dataset for any of the following reasons: gender discordance according to array data, call rate <95%, excess heterozygosity (<italic>P</italic> < 1 × 10<sup>−06</sup>), individuals not concordant with previous genotyping, discordant duplicate pairs, within-study duplicates with discordant phenotype data, or inter-study duplicates, first degree relatives, phenotypic exclusions and concordant replicates. Multi-dimensional scaling was used to infer ethnicity; individuals with greater than 15% mixed ancestry were excluded from analyses. Clustering of significantly associated, directly-genotyped SNPs was verified by manual inspection of genotype cluster plots (<ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Fig. S1</ext-link>). Of the 447 target-SNPs selected for fine-mapping, 424 passed post-genotyping quality control measures; we excluded six SNPs that were monomorphic in Europeans and a further six that showed strongly significant deviation of genotype frequencies from Hardy–Weinberg proportions in controls (<italic>P</italic> < 1 × 10<sup>−04</sup>).</p></sec><sec id="s4c"><title>Bioinformatics</title><p>We used publically available DNase hypersensitivity, transcription factor binding and histone modification ChIP-seq data from the ENCODE project (<xref rid="DDV035C24" ref-type="bibr">24</xref>) and elsewhere (<xref rid="DDV035C27" ref-type="bibr">27</xref>,<xref rid="DDV035C31" ref-type="bibr">31</xref>) to overlay functional annotations on the fine-mapping region and investigate enrichment of functional elements at associated loci. For the rs676256 locus we first identified a subset of polymorphisms that had <italic>r</italic><sup>2</sup> ≥ 0.8 with the lead SNP and then filtered the putative functional significance of variants by applying a heuristic score using RegulomeDB (<uri xlink:type="simple" xlink:href="http://regulome.stanford.edu/">http://regulome.stanford.edu/</uri>) to prioritise candidate functional variants prior to further investigation.</p></sec><sec id="s4d"><title>Quantitative 3C</title><p>MCF7 and SUM44 3C libraries were generated using 2 × 10<sup>7</sup> cells fixed with 2% paraformaldehyde for 5 min. 3C was carried out using the digestion and ligation steps of a Hi-C protocol (<xref rid="DDV035C45" ref-type="bibr">45</xref>), replacing the biotin dNTP fill-in with the addition of 56.7 µl of water. A control 3C library was generated as previously described (<xref rid="DDV035C46" ref-type="bibr">46</xref>) using minimally overlapping BAC clones (Children's Hospital Oakland Research Institute, Oakland CA; Life Technologies, Carlsbad, CA, USA) which covered the <italic>Hin</italic>dIII fragments between rs10816625 and the target region, combined in equimolar amounts. To optimise the Taqman PCR reactions and normalise the data, we generated a standard curve using the control templates. Taqman PCR was carried out using Taqman Universal PCR Mastermix no UNG (Life Technologies, Carlsbad CA) with 250 ng of 3C library. Three separate 3C libraries were prepared for each cell-line, then from each library three quantitative PCR reactions were performed for each restriction fragment. Interactions between rs10816625/rs13294895 and target loci were expressed as relative interaction frequencies compared with the control BAC library standard curve. BAC libraries and primer sequences are available on request.</p></sec><sec id="s4e"><title>Dual luciferase assays</title><p>DNA fragments containing either rs10816625 and rs13294895 or rs5899787 were cloned into the multiple cloning site of pGL4.23[luc2/minP] (Promega, Madison, WI). Site-directed mutagenesis with the Quickchange Lightning Site Directed Mutagenesis Kit (Agilent Technologies, Berkshire, UK) was used to create constructs containing all combinations of rs10816625/rs13294895 common and risk alleles (rs10286625 common/rs13294895 common, pGL4minP-AB; rs10286625 risk/rs13294895 common, pGL4minP-aB; rs10286625 common/rs13294895 risk, pGL4minP-Ab; rs10286625 risk/rs13294895 risk, pGL4minP-ab). In addition, we created reverse orientation constructs for each insert to verify orientation independence. The allelic status of each construct was confirmed by Sanger sequencing. PCR primers for cloning and site-directed mutagenesis are available on request. We used gBlocks Gene Fragments (Integrated DNA Technologies, Leuven, Belgium) to create constructs (pGL4minP-A and pGL4minP-a) for the common and risk alleles of the rs5899787 SNP.</p><p>MCF7 and T47D cells (ATCC, Middlesex, UK) were seeded at a density of 1.6 × 10<sup>04</sup> cells per well of a 96-well plate and transfected with 50 ng of pGL4.23[luc2/minP] or cloned constructs and 50 ng of pGL4.74[hRluc/TK] (Promega) using XtremeGENE HP transfection reagent (Roche, Basel, Switzerland). Luciferase levels were measured using a Victor luminometer (PerkinElmer, Waltham, MI) after 24 h using the Dual-Glo Luciferase Assay System (Promega). All transfections were repeated five times.</p></sec><sec id="s4f"><title>Statistics</title><p>Analysis of the association between each SNP and risk of breast cancer was performed using unconditional logistic regression assuming a log-additive genetic model, adjusted for study and ancestry-informative principal components (<italic>n</italic> = 7 for European studies; <italic>n</italic> = 2 for Asian and African studies). <italic>P</italic>-values were calculated using a one-degree of freedom likelihood-ratio test. We also estimated the effects of each heterozygote and minor-allele homozygote genotype relative to the common homozygote in a two-degrees-of-freedom model (<ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material, Table S2</ext-link>). Forward stepwise logistic regression was used to explore whether additional loci in the fine-mapping region were independently associated with breast cancer risk. <italic>I</italic><sup>2</sup> statistics were used to assess heterogeneity of the RR estimates between studies at significantly associated loci. We conducted analyses of SNP associations by tumour receptor status, morphology, lymph node involvement, grade and age for the European and Asian ancestry studies using polytomous logistic regression. Tumour information in BCAC was collected as previously described (<xref rid="DDV035C47" ref-type="bibr">47</xref>). There were too few samples with African ancestry to conduct stratified analyses. We also considered a polytomous logistic regression model comprising all four possible combinations of ER and PR status. Case-only analyses of tumour receptor status, morphology and lymph node involvement were used to assess heterogeneity between disease subtypes. Case-only allelic logistic regression using number of copies of each minor allele as response variable was used to test for linear trends in OR by grade and age at diagnosis.</p><p>We used a <italic>t</italic>-test to assess the difference in mean dual luciferase ratios for reporter gene constructs. One-way analysis of variance was used to assess equality of means of log-transformed dual luciferase ratios. Homogeneity of variances was assessed using Bartlett's test and QQ-plots of standardised residuals were visually inspected for evidence of departure from those expected under a normal distribution.</p><p>Post-hoc comparison of group means was carried out using Tukey's HSD test. All statistical analyses were conducted using R (<uri xlink:type="simple" xlink:href="www.R-project.org/">www.R-project.org/</uri>) and the Genotype Libraries and Utilities package (GLU; <uri xlink:type="simple" xlink:href="code.google.com/p/glu-genetics">code.google.com/p/glu-genetics</uri>).</p></sec></sec><sec id="s5"><title>Supplementary Material</title><p><ext-link ext-link-type="uri" xlink:href="http://hmg.oxfordjournals.org/lookup/suppl/doi:10.1093/hmg/ddv035/-/DC1">Supplementary Material is available at <italic>HMG</italic> online</ext-link>.</p></sec><sec id="s6"><title>Funding</title><p>BCAC is funded by <funding-source id="cs1" rid="cn1">Cancer Research UK</funding-source> (<award-id id="cn1" rid="cs1">C1287/A10118, C1287/A12014</award-id>) and by the <funding-source id="cs2" rid="cn2">European Community's Seventh Framework Programme</funding-source> under grant agreement number 223175 (grant number <award-id id="cn2" rid="cs2">HEALTH-F2-2009-223175</award-id>). Funding for the iCOGS infrastructure came from: <funding-source id="cs3" rid="cn3">the European Community's Seventh Framework Programme</funding-source> under grant agreement no. 223175 (<award-id id="cn3" rid="cs3">HEALTH-F2-2009-223175</award-id>) (COGS), <funding-source id="cs4" rid="cn4">Cancer Research UK</funding-source> (<award-id id="cn4" rid="cs4">C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565</award-id>), the <funding-source id="cs5" rid="cn5">National Institutes of Health</funding-source> (<award-id id="cn5" rid="cs5">CA128978</award-id>) and <funding-source id="cs6" rid="cn6">Post-Cancer GWAS initiative</funding-source> (<award-id id="cn6" rid="cs6">1U19 CA148537, 1U19 CA148065 and 1U19 CA148112</award-id>—the GAME-ON initiative), the <funding-source id="cs7" rid="cn7">Department of Defence</funding-source> (<award-id id="cn7" rid="cs7">W81XWH-10-1-0341</award-id>), the <funding-source id="cs8" rid="cn8">Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund</funding-source>. The Australian Breast Cancer Family Study (ABCFS) was supported by grant <award-id id="cn8" rid="cs8">UM1 CA164920</award-id> from the National Cancer Institute (USA). The ABCS study was supported by the <funding-source id="cs9" rid="cn9">Dutch Cancer Society</funding-source> (grants <award-id id="cn9" rid="cs9">NKI 2007-3839; 2009 4363</award-id>); BBMRI-NL, which is a Research Infrastructure financed by the <funding-source id="cs10" rid="cn10">Dutch government</funding-source> (<award-id id="cn10" rid="cs10">NWO 184.021.007</award-id>) and the Dutch National Genomics Initiative. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). E.S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas’ NHS Foundation Trust in partnership with King's College London, UK. I.T. is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Ligue contre le Cancer Grand Ouest, Agence Nationale de Sécurité Sanitaire (ANSES) Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Temática de Investigación Cooperativa en Cáncer and grants from the <funding-source id="cs11" rid="cn11">Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario</funding-source> (<award-id id="cn11" rid="cs11">PI11/00923 and PI081120</award-id>). The Human Genotyping-CEGEN Unit (CNIO) is supported by the Instituto de Salud Carlos III. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97–10500) and is currently funded through the <funding-source id="cs12" rid="cn12">National Institutes of Health</funding-source> (<award-id id="cn12" rid="cs12">R01 CA77398</award-id>). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. H.A.C receives support from the <funding-source id="cs13" rid="cn13">Lon V Smith Foundation</funding-source> (<award-id id="cn13" rid="cs13">LVS39420</award-id>). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC was supported by <funding-source id="cs14" rid="cn14">Deutsche Krebshilfe</funding-source> (<award-id id="cn14" rid="cs14">107 352</award-id>). The GENICA was funded by the <funding-source id="cs15" rid="cn15">Federal Ministry of Education and Research (BMBF) Germany</funding-source> grants <award-id id="cn15" rid="cs15">01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114</award-id>, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The HEBCS was financially supported by the <funding-source id="cs16" rid="cn16">Helsinki University Central Hospital Research Fund, Academy of Finland</funding-source> (<award-id id="cn16" rid="cs16">266528</award-id>), the Finnish Cancer Society, and The Nordic Cancer Union and the Sigrid Juselius Foundation. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, The Swedish Cancer Society and the Gustav V Jubilee foundation. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. ‘kConFab’ is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and <funding-source id="cs17" rid="cn17">the Cancer Foundation of Western Australia</funding-source>. LMBC is supported by the ‘Stichting tegen Kanker’ (<award-id id="cn17" rid="cs17">232–2008 and 196–2010</award-id>). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII. The MARIE study was supported by the <funding-source id="cs18" rid="cn18">Deutsche Krebshilfe e.V.</funding-source> [<award-id id="cn18" rid="cs18">70-2892-BR I</award-id>], the Hamburg Cancer Society, the German Cancer Research Center and the <funding-source id="cs19" rid="cn19">Federal Ministry of Education and Research (BMBF)</funding-source>, Germany (<award-id id="cn19" rid="cs19">01KH0402</award-id>). MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the <funding-source id="cs20" rid="cn20">Fondazione IRCCS Istituto Nazionale Tumori</funding-source>, according to Italian laws (INT—Institutional strategic projects ‘5 × 1000’). The MCBCS was supported by the NIH grants <award-id id="cn20" rid="cs20">CA128978, CA116167 and CA176785</award-id> and <funding-source id="cs21" rid="cn21">NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer</funding-source> (<award-id id="cn21" rid="cs21">CA116201</award-id>), and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian <funding-source id="cs22" rid="cn22">NHMRC</funding-source> grants <award-id id="cn22" rid="cs22">209057, 251553 and 504711</award-id> and by infrastructure provided by Cancer Council Victoria. The MEC was support by <funding-source id="cs23" rid="cn23">NIH</funding-source> grants <award-id id="cn23" rid="cs23">CA63464, CA54281, CA098758 and CA132839</award-id>. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, <funding-source id="cs24" rid="cn24">the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program</funding-source>—grant # <award-id id="cn24" rid="cs24">CRN-87521</award-id> and the <funding-source id="cs25" rid="cn25">Ministry of Economic Development, Innovation and Export Trade</funding-source>—grant # <award-id id="cn25" rid="cs25">PSR-SIIRI-701</award-id>. The NBCS was supported by grants from the <funding-source id="cs26" rid="cn26">Norwegian Research council</funding-source>, <award-id id="cn26" rid="cs26">155218/V40, 175240/S10</award-id> to A.L.B.D., <funding-source id="cs27" rid="cn27">FUGE-NFR</funding-source><award-id id="cn27" rid="cs27">181600/V11</award-id> to V.N.K. and a Swizz Bridge Award to A.L.B.D. The <funding-source id="cs28" rid="cn28">NBHS</funding-source> was supported by NIH grant <award-id id="cn28" rid="cs28">R01CA100374</award-id>. Biological sample preparation was conducted by the <funding-source id="cs29" rid="cn29">Survey and Biospecimen Shared Resource</funding-source>, which is supported by <award-id id="cn29" rid="cs29">P30 CA68485</award-id>. The OBCS was supported by research grants from <funding-source id="cs30" rid="cn30">the Finnish Cancer Foundation, the Academy of Finland</funding-source> (grant number <award-id id="cn30" rid="cs30">250083, 122715</award-id> and <funding-source id="cs31" rid="cn31">Center of Excellence</funding-source> grant number <award-id id="cn31" rid="cs31">251314</award-id>), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the <funding-source id="cs32" rid="cn32">University of Oulu Support Foundation</funding-source> and the special Governmental EVO funds for Oulu University Hospital-based research activities. OFBCR was supported by grant <award-id id="cn32" rid="cs32">UM1 CA164920</award-id> from the National Cancer Institute (USA). The ORIGO study was supported by the <funding-source id="cs33" rid="cn33">Dutch Cancer Society</funding-source> (<award-id id="cn33" rid="cs33">RUL 1997–1505</award-id>) and the <funding-source id="cs34" rid="cn34">Biobanking and Biomolecular Resources Research Infrastructure</funding-source> (<award-id id="cn34" rid="cs34">BBMRI-NL CP16</award-id>). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The pKARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The RBCS was funded by the <funding-source id="cs35" rid="cn35">Dutch Cancer Society</funding-source> (<award-id id="cn35" rid="cs35">DDHK 2004-3124, DDHK 2009-4318</award-id>). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCS was supported by <funding-source id="cs36" rid="cn36">Yorkshire Cancer Research</funding-source><award-id id="cn36" rid="cs36">S295, S299, S305PA</award-id>. SEARCH is funded by a programme grant from <funding-source id="cs37" rid="cn37">Cancer Research UK</funding-source> (<award-id id="cn37" rid="cs37">C490/A10124</award-id>) and supported by the <funding-source id="cs38" rid="cn38">UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge</funding-source>. The SZBCS was supported by Grant <award-id id="cn38" rid="cs38">PBZ_KBN_122/P05/2004</award-id>. SKKDKFZS is supported by the <funding-source id="cs39" rid="cn39">DKFZ</funding-source>. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (<award-id id="cn39" rid="cs39">CA116201</award-id>), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation, the Stefanie Spielman Breast Cancer fund and the OSU Comprehensive Cancer Center, <funding-source id="cs40" rid="cn40">DBBR</funding-source> (a CCSG Share Resource by National Institutes of Health Grant <award-id id="cn40" rid="cs40">P30 CA016056</award-id>), the <funding-source id="cs41" rid="cn41">Hellenic Cooperative Oncology Group</funding-source> research grant (<award-id id="cn41" rid="cs41">HR R_BG/04</award-id>) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, the European Union (European Social Fund—ESF), and Greek national funds through the Operational Program ‘Education and Lifelong Learning’ of the National Strategic Reference Framework (NSRF)—ARISTEIA. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The ACP study is funded by the Breast Cancer Research Trust, UK. The HERPACC was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by <funding-source id="cs42" rid="cn42">National Cancer Center Research and Development Fund</funding-source>. LAABC is supported by grants (<award-id id="cn42" rid="cs42">1RB-0287, 3PB-0102, 5PB-0018 and 10PB-0098</award-id>) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the <funding-source id="cs43" rid="cn43">California Department of Health</funding-source>. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number <award-id id="cn43" rid="cs43">N01CN25403</award-id>. MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), <funding-source id="cs44" rid="cn44">Malaysian Ministry of Higher Education</funding-source> (<award-id id="cn44" rid="cs44">UM.C/HlR/MOHE/06</award-id>) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the <funding-source id="cs45" rid="cn45">Biomedical Research Council</funding-source> (<award-id id="cn45" rid="cs45">BMRC08/1/35/19/550</award-id>), Singapore and the <funding-source id="cs46" rid="cn46">National Medical Research Council</funding-source>, Singapore (<award-id id="cn46" rid="cs46">NMRC/CG/SERI/2010</award-id>). The SBCGS was supported primarily by <funding-source id="cs47" rid="cn47">NIH</funding-source> grants <award-id id="cn47" rid="cs47">R01CA64277, R01CA148667 and R37CA70867</award-id>. Biological sample preparation was conducted by the <funding-source id="cs48" rid="cn48">Survey and Biospecimen Shared Resource</funding-source>, which is supported by <award-id id="cn48" rid="cs48">P30 CA68485</award-id>. The scientific development and funding of this project were, in part, supported by the <funding-source id="cs49" rid="cn49">Genetic Associations and Mechanisms in Oncology (GAME-ON) Network</funding-source><award-id id="cn49" rid="cs49">U19 CA148065</award-id>. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the <funding-source id="cs50" rid="cn50">Ministry of Education, Science and Technology</funding-source> (<award-id id="cn50" rid="cs50">2012-0000347</award-id>). SGBCC is funded by the <funding-source id="cs51" rid="cn51">National Medical Research Council start-up Grant and Centre</funding-source> Grant (<award-id id="cn51" rid="cs51">NMRC/CG/NCIS/2010</award-id>). Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the <funding-source id="cs52" rid="cn52">Biomedical Research Council</funding-source>, grant number: <award-id id="cn52" rid="cs52">05/1/21/19/425</award-id>. The TBCS was funded by The National Cancer Institute, Thailand. The TWBCS is supported by the <funding-source id="cs53" rid="cn53">Taiwan Biobank project of the Institute of Biomedical Sciences</funding-source>, Academia Sinica, Taiwan. The NBHS was supported by NIH grant <award-id id="cn53" rid="cs53">R01CA100374</award-id>. Biological sample preparation was conducted by the <funding-source id="cs54" rid="cn54">Survey and Biospecimen Shared Resource</funding-source>, which is supported by <award-id id="cn54" rid="cs54">P30 CA68485</award-id>. The SCCS is supported by a grant from the <funding-source id="cs55" rid="cn55">National Institutes of Health</funding-source> (<award-id id="cn55" rid="cs55">R01 CA092447</award-id>). The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Funding to pay the Open Access publication charges for this article was provided by the Charity Open Access Fund (COAF).</p></sec><sec sec-type="supplementary-material"><title>Supplementary Material</title><supplementary-material id="PMC_1" content-type="local-data"><caption><title>Supplementary Data</title></caption><media mimetype="text" mime-subtype="html" xlink:href="supp_24_10_2966__index.html"></media><media xlink:role="associated-file" mimetype="application" mime-subtype="msword" xlink:href="supp_ddv035_ddv035supp.docx"></media><media xlink:role="associated-file" mimetype="application" mime-subtype="msword" xlink:href="supp_ddv035_ddv035supp_tables.doc"></media></supplementary-material></sec></body><back><ack><title>Acknowledgements</title><p>BCAC thanks all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. The COGS study would not have been possible without the contributions of the following: Qin Wang (BCAC), Andrew Berchuck (OCAC), Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Antonis Antoniou, Lesley McGuffog, Fergus Couch and Ken Offit (CIMBA), Andrew Lee, Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, the staff of the CNIO genotyping unit, Sylvie LaBoissière and Frederic Robidoux and the staff of the McGill University and Génome Québec Innovation Centre, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. ABCFS thanks Maggie Angelakos, Judi Maskiell and Gillian Dite. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C.S. is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. ABCS thanks Sanquin Research Amsterdam, the Netherlands. BBCS thanks Eileen Williams, Elaine Ryder-Mills and Kara Sargus. BIGGS thanks Niall McInerney, Gabrielle Colleran, Andrew Rowan and Angela Jones. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CGPS thanks staff and participants of the Copenhagen General Population Study; for excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank and Dorthe Kjeldgård Hansen. CNIO-BCS thank Guillermo Pita, Charo Alonso, Daniel Herrero, Nuria Álvarez, Pilar Zamora, Primitiva Menendez and the Human Genotyping-CEGEN Unit (CNIO). The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, Yani Lu and Jessica Clague DeHart at the Beckman Research Institute of City of Hope; Dennis Deapen, Rich Pinder, Eunjung Lee and Fred Schumacher at the University of Southern California; Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California and Hoda Anton-Culver, Argyrios Ziogas and Hannah Park at the University of California Irvine. ESTHER thank Hartwig Ziegler, Sonja Wolf and Volker Hermann. GC-HBOC thank Heide Hellebrand, Stefanie Engert and GC-HBOC. The GENICA Network: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany; [HB, Wing-Yee Lo, Christina Justenhoven], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz] and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HEBCS thank Karl von Smitten and Irja Erkkilä. HMBCS thank Peter Hillemanns, Hans Christiansen and Johann H. Karstens. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. KBCP thank Eija Myöhänen and Helena Kemiläinen. kConFab/AOCS thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia and the National Institute of Health, USA) for their contributions to this resource, and the many families who contribute to kConFab. LMBC thank Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel and Kathleen Corthouts. MARIE thanks Alina Vrieling, Katharina Buck, Muhabbet Celik, Ursula Eilber and Sabine Behrens. MBCSG thank Siranoush Manoukian, Giulietta Scuvera and Daniela Zaffaroni of the Fondazione IRCCS Istituto Nazionale dei Tumori (INT); Bernardo Bonanni, Monica Barile and Irene Feroce of the Istituto Europeo di Oncologia (IEO) and Loris Bernard the personnel of the Cogentech Cancer Genetic Test Laboratory. MTLGEBCS would like to thank Martine Tranchant (Cancer Genomics Laboratory, CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thank study participants and research staff for their contributions and commitment to this study. The OBCS thanks Meeri Otsukka and Kari Mononen. The Ontario Familial Breast Cancer Registry, OFBCR, thanks Teresa Selander and Nayana Weerasooriya. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement by the USA Government or the BCFR. ORIGO thank E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires and managing clinical information. The LUMC survival data were retrieved from the Leiden hospital-based cancer registry system (ONCDOC) with the help of Dr J. Molenaar. The PBCS thank Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. pKARMA thank the Swedish Medical Research Council. The RBCS thank Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens and Annette Heemskerk, the Erasmus MC Family Cancer Clinic. SASBAC thank the Swedish Medical Research Council. SBCS thank Sue Higham, Helen Cramp, Ian Brock, Sabapathy Balasubramanian and Dan Connley. SEARCH thanks the SEARCH and EPIC teams. SKKDKFZS thank all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. The TNBCC thanks Robert Pilarski and Charles Shapiro who were instrumental in the formation of the OSU Breast Cancer Tissue Bank. We thank the Human Genetics Sample Bank for processing of samples and providing OSU Columbus area control samples. The UKBGS thank study participants, study staff and the doctors, nurses and other health care providers and health information sources who have contributed to the study. The ACP study wishes to thank the participants in the Thai Breast Cancer study. Special thanks also go to the Thai Ministry of Public Health (MOPH), doctors and nurses who helped with the data collection process. Finally, the ACP study thank Dr Prat Boonyawongviroj, the former Permanent Secretary of MOPH, and Dr Pornthep Siriwanarungsan, the Department Director-General of Disease Control who have supported the study throughout. LAABC thank all the study participants and the entire data collection team, especially Annie Fung and June Yashiki. MYBRCA thank Phuah Sze Yee, Peter Kang, Kang In Nee, Kavitta Sivanandan, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee, Teh Yew Ching and Nur Aishah Mohd Taib for DNA Extraction and patient recruitment. SBCGS thank study participants and research staff for their contributions and commitment to this study. The SGBCC would like to thank the participants and research coordinator Kimberley Chua. NBHS thanks study participants and research staff for their contributions and commitment to this study. Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). 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