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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk</title><author><name sortKey="Stevens, K N" sort="Stevens, K N" uniqKey="Stevens K" first="K N" last="Stevens">K N Stevens</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Garcia Closas, M" sort="Garcia Closas, M" uniqKey="Garcia Closas M" first="M" last="Garcia-Closas">M. Garcia-Closas</name><affiliation><nlm:aff id="aff2"><institution>Sections of Epidemiology and Genetics, Institute of Cancer Research and Breakthrough Breast Cancer Research Centre</institution>, 123 Old Brompton Road, London SW7 3RP,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Fredericksen, Z" sort="Fredericksen, Z" uniqKey="Fredericksen Z" first="Z" last="Fredericksen">Z. Fredericksen</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Kosel, M" sort="Kosel, M" uniqKey="Kosel M" first="M" last="Kosel">M. Kosel</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Pankratz, V S" sort="Pankratz, V S" uniqKey="Pankratz V" first="V S" last="Pankratz">V S Pankratz</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Hopper, J L" sort="Hopper, J L" uniqKey="Hopper J" first="J L" last="Hopper">J L Hopper</name><affiliation><nlm:aff id="aff3"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Dite, G S" sort="Dite, G S" uniqKey="Dite G" first="G S" last="Dite">G S Dite</name><affiliation><nlm:aff id="aff3"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Apicella, C" sort="Apicella, C" uniqKey="Apicella C" first="C" last="Apicella">C. Apicella</name><affiliation><nlm:aff id="aff3"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Southey, M C" sort="Southey, M C" uniqKey="Southey M" first="M C" last="Southey">M C Southey</name><affiliation><nlm:aff id="aff4"><institution>Department of Pathology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Schmidt, M K" sort="Schmidt, M K" uniqKey="Schmidt M" first="M K" last="Schmidt">M K Schmidt</name><affiliation><nlm:aff id="aff5"><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Broeks, A" sort="Broeks, A" uniqKey="Broeks A" first="A" last="Broeks">A. Broeks</name><affiliation><nlm:aff id="aff5"><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Van Veer, L J" sort="Van Veer, L J" uniqKey="Van Veer L" first="L J" last="Van Veer">L J Van Veer</name><affiliation><nlm:aff id="aff5"><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Tollenaar, R A E M" sort="Tollenaar, R A E M" uniqKey="Tollenaar R" first="R A E M" last="Tollenaar">R A E M. Tollenaar</name><affiliation><nlm:aff id="aff6"><institution>Leiden University Medical Center</institution>, Albinusdreef 2, 2333 ZA, Leiden,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Fasching, P A" sort="Fasching, P A" uniqKey="Fasching P" first="P A" last="Fasching">P A Fasching</name><affiliation><nlm:aff id="aff7"><institution>Division of Hematology and Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine</institution>, Los Angeles, CA 90095,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff8"><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Beckmann, M W" sort="Beckmann, M W" uniqKey="Beckmann M" first="M W" last="Beckmann">M W Beckmann</name><affiliation><nlm:aff id="aff8"><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hein, A" sort="Hein, A" uniqKey="Hein A" first="A" last="Hein">A. Hein</name><affiliation><nlm:aff id="aff8"><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Ekici, A B" sort="Ekici, A B" uniqKey="Ekici A" first="A B" last="Ekici">A B Ekici</name><affiliation><nlm:aff id="aff9"><institution>Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Johnson, N" sort="Johnson, N" uniqKey="Johnson N" first="N" last="Johnson">N. Johnson</name><affiliation><nlm:aff id="aff10"><institution>Breakthrough Breast Cancer Research Centre, Institute of Cancer Research</institution>, 123 Old Brompton Road, London SW7 3RP,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Peto, J" sort="Peto, J" uniqKey="Peto J" first="J" last="Peto">J. Peto</name><affiliation><nlm:aff id="aff11"><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Dos Santos Silva, I" sort="Dos Santos Silva, I" uniqKey="Dos Santos Silva I" first="I" last="Dos Santos Silva">I. Dos Santos Silva</name><affiliation><nlm:aff id="aff11"><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Gibson, L" sort="Gibson, L" uniqKey="Gibson L" first="L" last="Gibson">L. Gibson</name><affiliation><nlm:aff id="aff11"><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Sawyer, E" sort="Sawyer, E" uniqKey="Sawyer E" first="E" last="Sawyer">E. Sawyer</name><affiliation><nlm:aff id="aff12"><institution>National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust, Guy's Hospital</institution>, Great Maze Pond, London SE19RT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Tomlinson, I" sort="Tomlinson, I" uniqKey="Tomlinson I" first="I" last="Tomlinson">I. Tomlinson</name><affiliation><nlm:aff id="aff13"><institution>Oxford Biomedical Research Centre, Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford</institution>, Oxford OX3 7BN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Kerin, M J" sort="Kerin, M J" uniqKey="Kerin M" first="M J" last="Kerin">M J Kerin</name><affiliation><nlm:aff id="aff14"><institution>NUIG Department of Surgery, Clinical Science Institute, University Hospital Galway</institution>, Galway 091 524 411,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Chanock, S" sort="Chanock, S" uniqKey="Chanock S" first="S" last="Chanock">S. Chanock</name><affiliation><nlm:aff id="aff15"><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lissowska, J" sort="Lissowska, J" uniqKey="Lissowska J" first="J" last="Lissowska">J. Lissowska</name><affiliation><nlm:aff id="aff16"><institution>Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center, Institute of Oncology</institution>, 5 Roentgena Street, 02-781 Warsaw,<country>Poland</country></nlm:aff></affiliation></author><author><name sortKey="Hunter, D J" sort="Hunter, D J" uniqKey="Hunter D" first="D J" last="Hunter">D J Hunter</name><affiliation><nlm:aff id="aff17"><institution>Program in Molecular and Genetic Epidemiology, Harvard School of Public Health</institution>, 677 Huntington Avenue, Boston, MA 02115,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Hoover, R N" sort="Hoover, R N" uniqKey="Hoover R" first="R N" last="Hoover">R N Hoover</name><affiliation><nlm:aff id="aff15"><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Thomas, G D" sort="Thomas, G D" uniqKey="Thomas G" first="G D" last="Thomas">G D Thomas</name><affiliation><nlm:aff id="aff15"><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Milne, R L" sort="Milne, R L" uniqKey="Milne R" first="R L" last="Milne">R L Milne</name><affiliation><nlm:aff id="aff18"><institution>Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO)</institution>, Calle Melchor Fernández Almagro 3, Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Perez, Ji Arias" sort="Perez, Ji Arias" uniqKey="Perez J" first="Ji Arias" last="Pérez">Ji Arias Pérez</name><affiliation><nlm:aff id="aff19"><institution>Servicio de Cirugía General y Especialidades, Hospital Monte Naranco</institution>, Av. Doctores Fernández Vega 107, Oviedo 33012,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Gonzalez Neira, A" sort="Gonzalez Neira, A" uniqKey="Gonzalez Neira A" first="A" last="González-Neira">A. González-Neira</name><affiliation><nlm:aff id="aff20"><institution>Human Gentyping Unit (CeGen), Spanish National Cancer Research Centre (CNIO)</institution>, Madrid,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Benitez, J" sort="Benitez, J" uniqKey="Benitez J" first="J" last="Benítez">J. Benítez</name><affiliation><nlm:aff id="aff21"><institution>Human Genetics Group, Spanish National Cancer Research Centre (CNIO)</institution>, Calle Melchor Fernández Almagro 3, Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Burwinkel, B" sort="Burwinkel, B" uniqKey="Burwinkel B" first="B" last="Burwinkel">B. Burwinkel</name><affiliation><nlm:aff id="aff22"><institution>Department of Obstetrics and Gynecology, University Hospital Heidelberg</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff23"><institution>Molecular Epidemiology Group, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Meindl, A" sort="Meindl, A" uniqKey="Meindl A" first="A" last="Meindl">A. Meindl</name><affiliation><nlm:aff id="aff24"><institution>Department of Gynaecology and Obstetrics, Technical University of Munich</institution>, Arcisstraße 21, 80333 Munich,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Schmutzler, R K" sort="Schmutzler, R K" uniqKey="Schmutzler R" first="R K" last="Schmutzler">R K Schmutzler</name><affiliation><nlm:aff id="aff25"><institution>Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Center of Molecular Medicine Cologne (CMMC), University Hospital of Cologne</institution>, 50931 Cologne,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bartrar, C R" sort="Bartrar, C R" uniqKey="Bartrar C" first="C R" last="Bartrar">C R Bartrar</name><affiliation><nlm:aff id="aff26"><institution>Institute of Human Genetics, University of Heidelberg</institution>, Im Neuenheimer Feld 366, 69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hamann, U" sort="Hamann, U" uniqKey="Hamann U" first="U" last="Hamann">U. Hamann</name><affiliation><nlm:aff id="aff27"><institution>Deutsches Krebsforschungszentrum (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Ko, Y D" sort="Ko, Y D" uniqKey="Ko Y" first="Y D" last="Ko">Y D Ko</name><affiliation><nlm:aff id="aff28"><institution>Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Betriebsstätte Johanniter Krankenhaus</institution>, Johanniterstraße 3-5; 53113 Bonn,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bruning, T" sort="Bruning, T" uniqKey="Bruning T" first="T" last="Brüning">T. Brüning</name><affiliation><nlm:aff id="aff29"><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA)</institution>, Burkle-de-la-Camp-Platz 1, 44789 Bochum,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Chang Claude, J" sort="Chang Claude, J" uniqKey="Chang Claude J" first="J" last="Chang-Claude">J. Chang-Claude</name><affiliation><nlm:aff id="aff30"><institution>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hein, R" sort="Hein, R" uniqKey="Hein R" first="R" last="Hein">R. Hein</name><affiliation><nlm:aff id="aff30"><institution>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Wang Gohrke, S" sort="Wang Gohrke, S" uniqKey="Wang Gohrke S" first="S" last="Wang-Gohrke">S. Wang-Gohrke</name><affiliation><nlm:aff id="aff31"><institution>Department of Obstetrics and Gynecology, University of Ulm</institution>, Albert-Einstein-Allee 11, 89081 Ulm,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Dork, T" sort="Dork, T" uniqKey="Dork T" first="T" last="Dörk">T. Dörk</name><affiliation><nlm:aff id="aff32"><institution>Hannover Medical School, Gynaecology Research Unit</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Schurmann, P" sort="Schurmann, P" uniqKey="Schurmann P" first="P" last="Schürmann">P. Schürmann</name><affiliation><nlm:aff id="aff32"><institution>Hannover Medical School, Gynaecology Research Unit</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bremer, M" sort="Bremer, M" uniqKey="Bremer M" first="M" last="Bremer">M. Bremer</name><affiliation><nlm:aff id="aff33"><institution>Hannover Medical School, Clinics of Radiation Oncology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hillemanns, P" sort="Hillemanns, P" uniqKey="Hillemanns P" first="P" last="Hillemanns">P. Hillemanns</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bogdanova, N" sort="Bogdanova, N" uniqKey="Bogdanova N" first="N" last="Bogdanova">N. Bogdanova</name><affiliation><nlm:aff id="aff33"><institution>Hannover Medical School, Clinics of Radiation Oncology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Zalutsky, J V" sort="Zalutsky, J V" uniqKey="Zalutsky J" first="J V" last="Zalutsky">J V Zalutsky</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Rogov, Y I" sort="Rogov, Y I" uniqKey="Rogov Y" first="Y I" last="Rogov">Y I Rogov</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Antonenkova, N" sort="Antonenkova, N" uniqKey="Antonenkova N" first="N" last="Antonenkova">N. Antonenkova</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name><affiliation><nlm:aff id="aff35"><institution>Department of Molecular Medicine and Surgery, Karolinska Institutet</institution>, S17176 Stockholm,<country>Sweden</country></nlm:aff></affiliation></author><author><name sortKey="Margolin, S" sort="Margolin, S" uniqKey="Margolin S" first="S" last="Margolin">S. Margolin</name><affiliation><nlm:aff id="aff36"><institution>Department of Oncology Pathology, Karolinska Institutet</institution>, S17176 Stockholm,<country>Sweden</country></nlm:aff></affiliation></author><author><name sortKey="Mannermaa, A" sort="Mannermaa, A" uniqKey="Mannermaa A" first="A" last="Mannermaa">A. Mannermaa</name><affiliation><nlm:aff id="aff37"><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Kataja, V" sort="Kataja, V" uniqKey="Kataja V" first="V" last="Kataja">V. Kataja</name><affiliation><nlm:aff id="aff38"><institution>Institute of Clinical Medicine, Department of Oncology, University of Eastern Finland, Kuopio University Hospital</institution>, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Kosma, V M" sort="Kosma, V M" uniqKey="Kosma V" first="V-M" last="Kosma">V-M Kosma</name><affiliation><nlm:aff id="aff37"><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Hartikainen, J" sort="Hartikainen, J" uniqKey="Hartikainen J" first="J" last="Hartikainen">J. Hartikainen</name><affiliation><nlm:aff id="aff37"><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, G" sort="Chenevix Trench, G" uniqKey="Chenevix Trench G" first="G" last="Chenevix-Trench">G. Chenevix-Trench</name><affiliation><nlm:aff id="aff39"><institution>Queensland Institute of Medical Research</institution>, 300 Herston Road, Herston, QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Chen, X" sort="Chen, X" uniqKey="Chen X" first="X" last="Chen">X. Chen</name><affiliation><nlm:aff id="aff39"><institution>Queensland Institute of Medical Research</institution>, 300 Herston Road, Herston, QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Peterlongo, P" sort="Peterlongo, P" uniqKey="Peterlongo P" first="P" last="Peterlongo">P. Peterlongo</name><affiliation><nlm:aff id="aff40"><institution>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT) and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>; via Adamello, 16 - 20139 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Bonanni, B" sort="Bonanni, B" uniqKey="Bonanni B" first="B" last="Bonanni">B. Bonanni</name><affiliation><nlm:aff id="aff41"><institution>Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia</institution>, via Ripamonti 435, 20141 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Bernard, L" sort="Bernard, L" uniqKey="Bernard L" first="L" last="Bernard">L. Bernard</name><affiliation><nlm:aff id="aff42"><institution>Department of Experimental Oncology, Istituto Europeo di Oncologia and Consortium for Genomics Technology (Cogentech)</institution>; via Adamello, 16 - 20139 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Manoukian, S" sort="Manoukian, S" uniqKey="Manoukian S" first="S" last="Manoukian">S. Manoukian</name><affiliation><nlm:aff id="aff43"><institution>Unit of Medical Genetics, Department of Preventive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT)</institution>, via Venezian 1 - 20133 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Wang, X" sort="Wang, X" uniqKey="Wang X" first="X" last="Wang">X. Wang</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Cerhan, J" sort="Cerhan, J" uniqKey="Cerhan J" first="J" last="Cerhan">J. Cerhan</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Vachon, C M" sort="Vachon, C M" uniqKey="Vachon C" first="C M" last="Vachon">C M Vachon</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Olson, J" sort="Olson, J" uniqKey="Olson J" first="J" last="Olson">J. Olson</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Giles, G G" sort="Giles, G G" uniqKey="Giles G" first="G G" last="Giles">G G Giles</name><affiliation><nlm:aff id="aff44"><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Baglietto, L" sort="Baglietto, L" uniqKey="Baglietto L" first="L" last="Baglietto">L. Baglietto</name><affiliation><nlm:aff id="aff44"><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mclean, C A" sort="Mclean, C A" uniqKey="Mclean C" first="C A" last="Mclean">C A Mclean</name><affiliation><nlm:aff id="aff46"><institution>Department of Anatomical Pathology, The Alfred Hospital</institution>, Commercial Road, Prahran VIC 3181,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Severi, G" sort="Severi, G" uniqKey="Severi G" first="G" last="Severi">G. Severi</name><affiliation><nlm:aff id="aff44"><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="John, E M" sort="John, E M" uniqKey="John E" first="E M" last="John">E M John</name><affiliation><nlm:aff id="aff47"><institution>Department of Epidemiology, Cancer Prevention Institute of California</institution>, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Miron, A" sort="Miron, A" uniqKey="Miron A" first="A" last="Miron">A. Miron</name><affiliation><nlm:aff id="aff48"><institution>Department of Surgery, Dana-Farber Cancer Institute</institution>, 450 Brookline Avenue, Boston, MA 02215-5450,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Winqvist, R" sort="Winqvist, R" uniqKey="Winqvist R" first="R" last="Winqvist">R. Winqvist</name><affiliation><nlm:aff id="aff49"><institution>Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Pylk S, K" sort="Pylk S, K" uniqKey="Pylk S K" first="K" last="Pylk S">K. Pylk S</name><affiliation><nlm:aff id="aff49"><institution>Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Jukkola Vuorinen, A" sort="Jukkola Vuorinen, A" uniqKey="Jukkola Vuorinen A" first="A" last="Jukkola-Vuorinen">A. Jukkola-Vuorinen</name><affiliation><nlm:aff id="aff50"><institution>Department of Oncology, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Grip, M" sort="Grip, M" uniqKey="Grip M" first="M" last="Grip">M. Grip</name><affiliation><nlm:aff id="aff51"><institution>Department of Surgery, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Andrulis, I" sort="Andrulis, I" uniqKey="Andrulis I" first="I" last="Andrulis">I. Andrulis</name><affiliation><nlm:aff id="aff52"><institution>Ontario Cancer Genetics Network, Cancer Care Ontario</institution>, 620 University Avenue, Toronto, ON M5G 2C1 ON,<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff53"><institution>Fred A. Litwin Center for Cancer Genetics, Mount Sinai Hospital</institution>, 600 University Avenue, Toronto, ON M5G 1X5, ON<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff54"><institution>Department of Molecular Genetics, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Knight, J A" sort="Knight, J A" uniqKey="Knight J" first="J A" last="Knight">J A Knight</name><affiliation><nlm:aff id="aff55"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, 600 University Avenue, Toronto, ON M5G 1X5 ON,<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff56"><institution>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Glendon, G" sort="Glendon, G" uniqKey="Glendon G" first="G" last="Glendon">G. Glendon</name><affiliation><nlm:aff id="aff52"><institution>Ontario Cancer Genetics Network, Cancer Care Ontario</institution>, 620 University Avenue, Toronto, ON M5G 2C1 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Mulligan, A M" sort="Mulligan, A M" uniqKey="Mulligan A" first="A M" last="Mulligan">A M Mulligan</name><affiliation><nlm:aff id="aff57"><institution>Department of Laboratory Medicine and Pathobiology, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff58"><institution>Department of Laboratory Medicine and Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital</institution>, 30 Bond Street, Toronto, ON M5B 1W8 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Cox, A" sort="Cox, A" uniqKey="Cox A" first="A" last="Cox">A. Cox</name><affiliation><nlm:aff id="aff59"><institution>Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Brock, I W" sort="Brock, I W" uniqKey="Brock I" first="I W" last="Brock">I W Brock</name><affiliation><nlm:aff id="aff59"><institution>Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Elliott, G" sort="Elliott, G" uniqKey="Elliott G" first="G" last="Elliott">G. Elliott</name><affiliation><nlm:aff id="aff60"><institution>Medical Genetics Research Group, Faculty of Medicine and Human Sciences, University of Manchester</institution>, Oxford Road, Manchester M13 9PL,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cross, S S" sort="Cross, S S" uniqKey="Cross S" first="S S" last="Cross">S S Cross</name><affiliation><nlm:aff id="aff61"><institution>Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Pharoah, P P" sort="Pharoah, P P" uniqKey="Pharoah P" first="P P" last="Pharoah">P P Pharoah</name><affiliation><nlm:aff id="aff62"><institution>United Kingdom Department of Oncology and Department of Public Health and Primary Care University of Cambridge</institution>, Cambridge,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Dunning, A M" sort="Dunning, A M" uniqKey="Dunning A" first="A M" last="Dunning">A M Dunning</name><affiliation><nlm:aff id="aff63"><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Pooley, K A" sort="Pooley, K A" uniqKey="Pooley K" first="K A" last="Pooley">K A Pooley</name><affiliation><nlm:aff id="aff63"><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Humphreys, M K" sort="Humphreys, M K" uniqKey="Humphreys M" first="M K" last="Humphreys">M K Humphreys</name><affiliation><nlm:aff id="aff64"><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Wang, J" sort="Wang, J" uniqKey="Wang J" first="J" last="Wang">J. Wang</name><affiliation><nlm:aff id="aff64"><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Kang, D" sort="Kang, D" uniqKey="Kang D" first="D" last="Kang">D. Kang</name><affiliation><nlm:aff id="aff65"><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></nlm:aff></affiliation></author><author><name sortKey="Yoo, K Y" sort="Yoo, K Y" uniqKey="Yoo K" first="K-Y" last="Yoo">K-Y Yoo</name><affiliation><nlm:aff id="aff65"><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></nlm:aff></affiliation></author><author><name sortKey="Noh, D Y" sort="Noh, D Y" uniqKey="Noh D" first="D-Y" last="Noh">D-Y Noh</name><affiliation><nlm:aff id="aff65"><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></nlm:aff></affiliation></author><author><name sortKey="Sangrajrang, S" sort="Sangrajrang, S" uniqKey="Sangrajrang S" first="S" last="Sangrajrang">S. Sangrajrang</name><affiliation><nlm:aff id="aff66"><institution>National Cancer Institute</institution>, Rama 6 Road, 10400 Bangkok,<country>Thailand</country></nlm:aff></affiliation></author><author><name sortKey="Gabrieau, V" sort="Gabrieau, V" uniqKey="Gabrieau V" first="V" last="Gabrieau">V. Gabrieau</name><affiliation><nlm:aff id="aff67"><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Brennan, P" sort="Brennan, P" uniqKey="Brennan P" first="P" last="Brennan">P. Brennan</name><affiliation><nlm:aff id="aff67"><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Mckay, J" sort="Mckay, J" uniqKey="Mckay J" first="J" last="Mckay">J. Mckay</name><affiliation><nlm:aff id="aff67"><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Anton Culver, H" sort="Anton Culver, H" uniqKey="Anton Culver H" first="H" last="Anton-Culver">H. Anton-Culver</name><affiliation><nlm:aff id="aff68"><institution>Department of Epidemiology, School of Medicine, University of California Irvine</institution>, 224 Irvine Hall, Irvine, CA 92697,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Ziogas, A" sort="Ziogas, A" uniqKey="Ziogas A" first="A" last="Ziogas">A. Ziogas</name><affiliation><nlm:aff id="aff68"><institution>Department of Epidemiology, School of Medicine, University of California Irvine</institution>, 224 Irvine Hall, Irvine, CA 92697,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Couch, F J" sort="Couch, F J" uniqKey="Couch F" first="F J" last="Couch">F J Couch</name><affiliation><nlm:aff id="aff69"><institution>Department of Laboratory Medicine and Pathology, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Easton, D F" sort="Easton, D F" uniqKey="Easton D" first="D F" last="Easton">D F Easton</name><affiliation><nlm:aff id="aff63"><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff64"><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22033276</idno><idno type="pmc">3251877</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251877</idno><idno type="RBID">PMC:3251877</idno><idno type="doi">10.1038/bjc.2011.448</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000093</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000093</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk</title><author><name sortKey="Stevens, K N" sort="Stevens, K N" uniqKey="Stevens K" first="K N" last="Stevens">K N Stevens</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Garcia Closas, M" sort="Garcia Closas, M" uniqKey="Garcia Closas M" first="M" last="Garcia-Closas">M. Garcia-Closas</name><affiliation><nlm:aff id="aff2"><institution>Sections of Epidemiology and Genetics, Institute of Cancer Research and Breakthrough Breast Cancer Research Centre</institution>, 123 Old Brompton Road, London SW7 3RP,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Fredericksen, Z" sort="Fredericksen, Z" uniqKey="Fredericksen Z" first="Z" last="Fredericksen">Z. Fredericksen</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Kosel, M" sort="Kosel, M" uniqKey="Kosel M" first="M" last="Kosel">M. Kosel</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Pankratz, V S" sort="Pankratz, V S" uniqKey="Pankratz V" first="V S" last="Pankratz">V S Pankratz</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Hopper, J L" sort="Hopper, J L" uniqKey="Hopper J" first="J L" last="Hopper">J L Hopper</name><affiliation><nlm:aff id="aff3"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Dite, G S" sort="Dite, G S" uniqKey="Dite G" first="G S" last="Dite">G S Dite</name><affiliation><nlm:aff id="aff3"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Apicella, C" sort="Apicella, C" uniqKey="Apicella C" first="C" last="Apicella">C. Apicella</name><affiliation><nlm:aff id="aff3"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Southey, M C" sort="Southey, M C" uniqKey="Southey M" first="M C" last="Southey">M C Southey</name><affiliation><nlm:aff id="aff4"><institution>Department of Pathology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Schmidt, M K" sort="Schmidt, M K" uniqKey="Schmidt M" first="M K" last="Schmidt">M K Schmidt</name><affiliation><nlm:aff id="aff5"><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Broeks, A" sort="Broeks, A" uniqKey="Broeks A" first="A" last="Broeks">A. Broeks</name><affiliation><nlm:aff id="aff5"><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Van Veer, L J" sort="Van Veer, L J" uniqKey="Van Veer L" first="L J" last="Van Veer">L J Van Veer</name><affiliation><nlm:aff id="aff5"><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Tollenaar, R A E M" sort="Tollenaar, R A E M" uniqKey="Tollenaar R" first="R A E M" last="Tollenaar">R A E M. Tollenaar</name><affiliation><nlm:aff id="aff6"><institution>Leiden University Medical Center</institution>, Albinusdreef 2, 2333 ZA, Leiden,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Fasching, P A" sort="Fasching, P A" uniqKey="Fasching P" first="P A" last="Fasching">P A Fasching</name><affiliation><nlm:aff id="aff7"><institution>Division of Hematology and Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine</institution>, Los Angeles, CA 90095,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff8"><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Beckmann, M W" sort="Beckmann, M W" uniqKey="Beckmann M" first="M W" last="Beckmann">M W Beckmann</name><affiliation><nlm:aff id="aff8"><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hein, A" sort="Hein, A" uniqKey="Hein A" first="A" last="Hein">A. Hein</name><affiliation><nlm:aff id="aff8"><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Ekici, A B" sort="Ekici, A B" uniqKey="Ekici A" first="A B" last="Ekici">A B Ekici</name><affiliation><nlm:aff id="aff9"><institution>Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Johnson, N" sort="Johnson, N" uniqKey="Johnson N" first="N" last="Johnson">N. Johnson</name><affiliation><nlm:aff id="aff10"><institution>Breakthrough Breast Cancer Research Centre, Institute of Cancer Research</institution>, 123 Old Brompton Road, London SW7 3RP,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Peto, J" sort="Peto, J" uniqKey="Peto J" first="J" last="Peto">J. Peto</name><affiliation><nlm:aff id="aff11"><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Dos Santos Silva, I" sort="Dos Santos Silva, I" uniqKey="Dos Santos Silva I" first="I" last="Dos Santos Silva">I. Dos Santos Silva</name><affiliation><nlm:aff id="aff11"><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Gibson, L" sort="Gibson, L" uniqKey="Gibson L" first="L" last="Gibson">L. Gibson</name><affiliation><nlm:aff id="aff11"><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Sawyer, E" sort="Sawyer, E" uniqKey="Sawyer E" first="E" last="Sawyer">E. Sawyer</name><affiliation><nlm:aff id="aff12"><institution>National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust, Guy's Hospital</institution>, Great Maze Pond, London SE19RT,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Tomlinson, I" sort="Tomlinson, I" uniqKey="Tomlinson I" first="I" last="Tomlinson">I. Tomlinson</name><affiliation><nlm:aff id="aff13"><institution>Oxford Biomedical Research Centre, Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford</institution>, Oxford OX3 7BN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Kerin, M J" sort="Kerin, M J" uniqKey="Kerin M" first="M J" last="Kerin">M J Kerin</name><affiliation><nlm:aff id="aff14"><institution>NUIG Department of Surgery, Clinical Science Institute, University Hospital Galway</institution>, Galway 091 524 411,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Chanock, S" sort="Chanock, S" uniqKey="Chanock S" first="S" last="Chanock">S. Chanock</name><affiliation><nlm:aff id="aff15"><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lissowska, J" sort="Lissowska, J" uniqKey="Lissowska J" first="J" last="Lissowska">J. Lissowska</name><affiliation><nlm:aff id="aff16"><institution>Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center, Institute of Oncology</institution>, 5 Roentgena Street, 02-781 Warsaw,<country>Poland</country></nlm:aff></affiliation></author><author><name sortKey="Hunter, D J" sort="Hunter, D J" uniqKey="Hunter D" first="D J" last="Hunter">D J Hunter</name><affiliation><nlm:aff id="aff17"><institution>Program in Molecular and Genetic Epidemiology, Harvard School of Public Health</institution>, 677 Huntington Avenue, Boston, MA 02115,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Hoover, R N" sort="Hoover, R N" uniqKey="Hoover R" first="R N" last="Hoover">R N Hoover</name><affiliation><nlm:aff id="aff15"><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Thomas, G D" sort="Thomas, G D" uniqKey="Thomas G" first="G D" last="Thomas">G D Thomas</name><affiliation><nlm:aff id="aff15"><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Milne, R L" sort="Milne, R L" uniqKey="Milne R" first="R L" last="Milne">R L Milne</name><affiliation><nlm:aff id="aff18"><institution>Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO)</institution>, Calle Melchor Fernández Almagro 3, Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Perez, Ji Arias" sort="Perez, Ji Arias" uniqKey="Perez J" first="Ji Arias" last="Pérez">Ji Arias Pérez</name><affiliation><nlm:aff id="aff19"><institution>Servicio de Cirugía General y Especialidades, Hospital Monte Naranco</institution>, Av. Doctores Fernández Vega 107, Oviedo 33012,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Gonzalez Neira, A" sort="Gonzalez Neira, A" uniqKey="Gonzalez Neira A" first="A" last="González-Neira">A. González-Neira</name><affiliation><nlm:aff id="aff20"><institution>Human Gentyping Unit (CeGen), Spanish National Cancer Research Centre (CNIO)</institution>, Madrid,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Benitez, J" sort="Benitez, J" uniqKey="Benitez J" first="J" last="Benítez">J. Benítez</name><affiliation><nlm:aff id="aff21"><institution>Human Genetics Group, Spanish National Cancer Research Centre (CNIO)</institution>, Calle Melchor Fernández Almagro 3, Madrid 28029,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Burwinkel, B" sort="Burwinkel, B" uniqKey="Burwinkel B" first="B" last="Burwinkel">B. Burwinkel</name><affiliation><nlm:aff id="aff22"><institution>Department of Obstetrics and Gynecology, University Hospital Heidelberg</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff23"><institution>Molecular Epidemiology Group, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Meindl, A" sort="Meindl, A" uniqKey="Meindl A" first="A" last="Meindl">A. Meindl</name><affiliation><nlm:aff id="aff24"><institution>Department of Gynaecology and Obstetrics, Technical University of Munich</institution>, Arcisstraße 21, 80333 Munich,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Schmutzler, R K" sort="Schmutzler, R K" uniqKey="Schmutzler R" first="R K" last="Schmutzler">R K Schmutzler</name><affiliation><nlm:aff id="aff25"><institution>Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Center of Molecular Medicine Cologne (CMMC), University Hospital of Cologne</institution>, 50931 Cologne,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bartrar, C R" sort="Bartrar, C R" uniqKey="Bartrar C" first="C R" last="Bartrar">C R Bartrar</name><affiliation><nlm:aff id="aff26"><institution>Institute of Human Genetics, University of Heidelberg</institution>, Im Neuenheimer Feld 366, 69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hamann, U" sort="Hamann, U" uniqKey="Hamann U" first="U" last="Hamann">U. Hamann</name><affiliation><nlm:aff id="aff27"><institution>Deutsches Krebsforschungszentrum (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Ko, Y D" sort="Ko, Y D" uniqKey="Ko Y" first="Y D" last="Ko">Y D Ko</name><affiliation><nlm:aff id="aff28"><institution>Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Betriebsstätte Johanniter Krankenhaus</institution>, Johanniterstraße 3-5; 53113 Bonn,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bruning, T" sort="Bruning, T" uniqKey="Bruning T" first="T" last="Brüning">T. Brüning</name><affiliation><nlm:aff id="aff29"><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA)</institution>, Burkle-de-la-Camp-Platz 1, 44789 Bochum,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Chang Claude, J" sort="Chang Claude, J" uniqKey="Chang Claude J" first="J" last="Chang-Claude">J. Chang-Claude</name><affiliation><nlm:aff id="aff30"><institution>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hein, R" sort="Hein, R" uniqKey="Hein R" first="R" last="Hein">R. Hein</name><affiliation><nlm:aff id="aff30"><institution>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Wang Gohrke, S" sort="Wang Gohrke, S" uniqKey="Wang Gohrke S" first="S" last="Wang-Gohrke">S. Wang-Gohrke</name><affiliation><nlm:aff id="aff31"><institution>Department of Obstetrics and Gynecology, University of Ulm</institution>, Albert-Einstein-Allee 11, 89081 Ulm,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Dork, T" sort="Dork, T" uniqKey="Dork T" first="T" last="Dörk">T. Dörk</name><affiliation><nlm:aff id="aff32"><institution>Hannover Medical School, Gynaecology Research Unit</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Schurmann, P" sort="Schurmann, P" uniqKey="Schurmann P" first="P" last="Schürmann">P. Schürmann</name><affiliation><nlm:aff id="aff32"><institution>Hannover Medical School, Gynaecology Research Unit</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bremer, M" sort="Bremer, M" uniqKey="Bremer M" first="M" last="Bremer">M. Bremer</name><affiliation><nlm:aff id="aff33"><institution>Hannover Medical School, Clinics of Radiation Oncology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Hillemanns, P" sort="Hillemanns, P" uniqKey="Hillemanns P" first="P" last="Hillemanns">P. Hillemanns</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Bogdanova, N" sort="Bogdanova, N" uniqKey="Bogdanova N" first="N" last="Bogdanova">N. Bogdanova</name><affiliation><nlm:aff id="aff33"><institution>Hannover Medical School, Clinics of Radiation Oncology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Zalutsky, J V" sort="Zalutsky, J V" uniqKey="Zalutsky J" first="J V" last="Zalutsky">J V Zalutsky</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Rogov, Y I" sort="Rogov, Y I" uniqKey="Rogov Y" first="Y I" last="Rogov">Y I Rogov</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Antonenkova, N" sort="Antonenkova, N" uniqKey="Antonenkova N" first="N" last="Antonenkova">N. Antonenkova</name><affiliation><nlm:aff id="aff34"><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name><affiliation><nlm:aff id="aff35"><institution>Department of Molecular Medicine and Surgery, Karolinska Institutet</institution>, S17176 Stockholm,<country>Sweden</country></nlm:aff></affiliation></author><author><name sortKey="Margolin, S" sort="Margolin, S" uniqKey="Margolin S" first="S" last="Margolin">S. Margolin</name><affiliation><nlm:aff id="aff36"><institution>Department of Oncology Pathology, Karolinska Institutet</institution>, S17176 Stockholm,<country>Sweden</country></nlm:aff></affiliation></author><author><name sortKey="Mannermaa, A" sort="Mannermaa, A" uniqKey="Mannermaa A" first="A" last="Mannermaa">A. Mannermaa</name><affiliation><nlm:aff id="aff37"><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Kataja, V" sort="Kataja, V" uniqKey="Kataja V" first="V" last="Kataja">V. Kataja</name><affiliation><nlm:aff id="aff38"><institution>Institute of Clinical Medicine, Department of Oncology, University of Eastern Finland, Kuopio University Hospital</institution>, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Kosma, V M" sort="Kosma, V M" uniqKey="Kosma V" first="V-M" last="Kosma">V-M Kosma</name><affiliation><nlm:aff id="aff37"><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Hartikainen, J" sort="Hartikainen, J" uniqKey="Hartikainen J" first="J" last="Hartikainen">J. Hartikainen</name><affiliation><nlm:aff id="aff37"><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, G" sort="Chenevix Trench, G" uniqKey="Chenevix Trench G" first="G" last="Chenevix-Trench">G. Chenevix-Trench</name><affiliation><nlm:aff id="aff39"><institution>Queensland Institute of Medical Research</institution>, 300 Herston Road, Herston, QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Chen, X" sort="Chen, X" uniqKey="Chen X" first="X" last="Chen">X. Chen</name><affiliation><nlm:aff id="aff39"><institution>Queensland Institute of Medical Research</institution>, 300 Herston Road, Herston, QLD 4029,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Peterlongo, P" sort="Peterlongo, P" uniqKey="Peterlongo P" first="P" last="Peterlongo">P. Peterlongo</name><affiliation><nlm:aff id="aff40"><institution>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT) and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>; via Adamello, 16 - 20139 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Bonanni, B" sort="Bonanni, B" uniqKey="Bonanni B" first="B" last="Bonanni">B. Bonanni</name><affiliation><nlm:aff id="aff41"><institution>Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia</institution>, via Ripamonti 435, 20141 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Bernard, L" sort="Bernard, L" uniqKey="Bernard L" first="L" last="Bernard">L. Bernard</name><affiliation><nlm:aff id="aff42"><institution>Department of Experimental Oncology, Istituto Europeo di Oncologia and Consortium for Genomics Technology (Cogentech)</institution>; via Adamello, 16 - 20139 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Manoukian, S" sort="Manoukian, S" uniqKey="Manoukian S" first="S" last="Manoukian">S. Manoukian</name><affiliation><nlm:aff id="aff43"><institution>Unit of Medical Genetics, Department of Preventive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT)</institution>, via Venezian 1 - 20133 Milano,<country>Italy</country></nlm:aff></affiliation></author><author><name sortKey="Wang, X" sort="Wang, X" uniqKey="Wang X" first="X" last="Wang">X. Wang</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Cerhan, J" sort="Cerhan, J" uniqKey="Cerhan J" first="J" last="Cerhan">J. Cerhan</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Vachon, C M" sort="Vachon, C M" uniqKey="Vachon C" first="C M" last="Vachon">C M Vachon</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Olson, J" sort="Olson, J" uniqKey="Olson J" first="J" last="Olson">J. Olson</name><affiliation><nlm:aff id="aff1"><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Giles, G G" sort="Giles, G G" uniqKey="Giles G" first="G G" last="Giles">G G Giles</name><affiliation><nlm:aff id="aff44"><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Baglietto, L" sort="Baglietto, L" uniqKey="Baglietto L" first="L" last="Baglietto">L. Baglietto</name><affiliation><nlm:aff id="aff44"><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mclean, C A" sort="Mclean, C A" uniqKey="Mclean C" first="C A" last="Mclean">C A Mclean</name><affiliation><nlm:aff id="aff46"><institution>Department of Anatomical Pathology, The Alfred Hospital</institution>, Commercial Road, Prahran VIC 3181,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Severi, G" sort="Severi, G" uniqKey="Severi G" first="G" last="Severi">G. Severi</name><affiliation><nlm:aff id="aff44"><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="John, E M" sort="John, E M" uniqKey="John E" first="E M" last="John">E M John</name><affiliation><nlm:aff id="aff47"><institution>Department of Epidemiology, Cancer Prevention Institute of California</institution>, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Miron, A" sort="Miron, A" uniqKey="Miron A" first="A" last="Miron">A. Miron</name><affiliation><nlm:aff id="aff48"><institution>Department of Surgery, Dana-Farber Cancer Institute</institution>, 450 Brookline Avenue, Boston, MA 02215-5450,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Winqvist, R" sort="Winqvist, R" uniqKey="Winqvist R" first="R" last="Winqvist">R. Winqvist</name><affiliation><nlm:aff id="aff49"><institution>Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Pylk S, K" sort="Pylk S, K" uniqKey="Pylk S K" first="K" last="Pylk S">K. Pylk S</name><affiliation><nlm:aff id="aff49"><institution>Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Jukkola Vuorinen, A" sort="Jukkola Vuorinen, A" uniqKey="Jukkola Vuorinen A" first="A" last="Jukkola-Vuorinen">A. Jukkola-Vuorinen</name><affiliation><nlm:aff id="aff50"><institution>Department of Oncology, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Grip, M" sort="Grip, M" uniqKey="Grip M" first="M" last="Grip">M. Grip</name><affiliation><nlm:aff id="aff51"><institution>Department of Surgery, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Andrulis, I" sort="Andrulis, I" uniqKey="Andrulis I" first="I" last="Andrulis">I. Andrulis</name><affiliation><nlm:aff id="aff52"><institution>Ontario Cancer Genetics Network, Cancer Care Ontario</institution>, 620 University Avenue, Toronto, ON M5G 2C1 ON,<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff53"><institution>Fred A. Litwin Center for Cancer Genetics, Mount Sinai Hospital</institution>, 600 University Avenue, Toronto, ON M5G 1X5, ON<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff54"><institution>Department of Molecular Genetics, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Knight, J A" sort="Knight, J A" uniqKey="Knight J" first="J A" last="Knight">J A Knight</name><affiliation><nlm:aff id="aff55"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, 600 University Avenue, Toronto, ON M5G 1X5 ON,<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff56"><institution>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Glendon, G" sort="Glendon, G" uniqKey="Glendon G" first="G" last="Glendon">G. Glendon</name><affiliation><nlm:aff id="aff52"><institution>Ontario Cancer Genetics Network, Cancer Care Ontario</institution>, 620 University Avenue, Toronto, ON M5G 2C1 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Mulligan, A M" sort="Mulligan, A M" uniqKey="Mulligan A" first="A M" last="Mulligan">A M Mulligan</name><affiliation><nlm:aff id="aff57"><institution>Department of Laboratory Medicine and Pathobiology, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff58"><institution>Department of Laboratory Medicine and Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital</institution>, 30 Bond Street, Toronto, ON M5B 1W8 ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Cox, A" sort="Cox, A" uniqKey="Cox A" first="A" last="Cox">A. Cox</name><affiliation><nlm:aff id="aff59"><institution>Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Brock, I W" sort="Brock, I W" uniqKey="Brock I" first="I W" last="Brock">I W Brock</name><affiliation><nlm:aff id="aff59"><institution>Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Elliott, G" sort="Elliott, G" uniqKey="Elliott G" first="G" last="Elliott">G. Elliott</name><affiliation><nlm:aff id="aff60"><institution>Medical Genetics Research Group, Faculty of Medicine and Human Sciences, University of Manchester</institution>, Oxford Road, Manchester M13 9PL,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cross, S S" sort="Cross, S S" uniqKey="Cross S" first="S S" last="Cross">S S Cross</name><affiliation><nlm:aff id="aff61"><institution>Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Pharoah, P P" sort="Pharoah, P P" uniqKey="Pharoah P" first="P P" last="Pharoah">P P Pharoah</name><affiliation><nlm:aff id="aff62"><institution>United Kingdom Department of Oncology and Department of Public Health and Primary Care University of Cambridge</institution>, Cambridge,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Dunning, A M" sort="Dunning, A M" uniqKey="Dunning A" first="A M" last="Dunning">A M Dunning</name><affiliation><nlm:aff id="aff63"><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Pooley, K A" sort="Pooley, K A" uniqKey="Pooley K" first="K A" last="Pooley">K A Pooley</name><affiliation><nlm:aff id="aff63"><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Humphreys, M K" sort="Humphreys, M K" uniqKey="Humphreys M" first="M K" last="Humphreys">M K Humphreys</name><affiliation><nlm:aff id="aff64"><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Wang, J" sort="Wang, J" uniqKey="Wang J" first="J" last="Wang">J. Wang</name><affiliation><nlm:aff id="aff64"><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Kang, D" sort="Kang, D" uniqKey="Kang D" first="D" last="Kang">D. Kang</name><affiliation><nlm:aff id="aff65"><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></nlm:aff></affiliation></author><author><name sortKey="Yoo, K Y" sort="Yoo, K Y" uniqKey="Yoo K" first="K-Y" last="Yoo">K-Y Yoo</name><affiliation><nlm:aff id="aff65"><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></nlm:aff></affiliation></author><author><name sortKey="Noh, D Y" sort="Noh, D Y" uniqKey="Noh D" first="D-Y" last="Noh">D-Y Noh</name><affiliation><nlm:aff id="aff65"><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></nlm:aff></affiliation></author><author><name sortKey="Sangrajrang, S" sort="Sangrajrang, S" uniqKey="Sangrajrang S" first="S" last="Sangrajrang">S. Sangrajrang</name><affiliation><nlm:aff id="aff66"><institution>National Cancer Institute</institution>, Rama 6 Road, 10400 Bangkok,<country>Thailand</country></nlm:aff></affiliation></author><author><name sortKey="Gabrieau, V" sort="Gabrieau, V" uniqKey="Gabrieau V" first="V" last="Gabrieau">V. Gabrieau</name><affiliation><nlm:aff id="aff67"><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Brennan, P" sort="Brennan, P" uniqKey="Brennan P" first="P" last="Brennan">P. Brennan</name><affiliation><nlm:aff id="aff67"><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Mckay, J" sort="Mckay, J" uniqKey="Mckay J" first="J" last="Mckay">J. Mckay</name><affiliation><nlm:aff id="aff67"><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Anton Culver, H" sort="Anton Culver, H" uniqKey="Anton Culver H" first="H" last="Anton-Culver">H. Anton-Culver</name><affiliation><nlm:aff id="aff68"><institution>Department of Epidemiology, School of Medicine, University of California Irvine</institution>, 224 Irvine Hall, Irvine, CA 92697,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Ziogas, A" sort="Ziogas, A" uniqKey="Ziogas A" first="A" last="Ziogas">A. Ziogas</name><affiliation><nlm:aff id="aff68"><institution>Department of Epidemiology, School of Medicine, University of California Irvine</institution>, 224 Irvine Hall, Irvine, CA 92697,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Couch, F J" sort="Couch, F J" uniqKey="Couch F" first="F J" last="Couch">F J Couch</name><affiliation><nlm:aff id="aff69"><institution>Department of Laboratory Medicine and Pathology, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Easton, D F" sort="Easton, D F" uniqKey="Easton D" first="D F" last="Easton">D F Easton</name><affiliation><nlm:aff id="aff63"><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff64"><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></nlm:aff></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (<italic>PIK3CA</italic>) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.</p></sec><sec><title>Methods:</title><p>A single-nucleotide polymorphism from the <italic>PIK3CA</italic> locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).</p></sec><sec><title>Results:</title><p>Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95–0.99, <italic>P</italic>=4.6 × 10<sup>−3</sup>), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96–1.01, <italic>P</italic>=0.139).</p></sec><sec><title>Conclusion:</title><p>Common germline variation in <italic>PIK3CA</italic> does not have a strong influence on the risk of breast cancer</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aleskandarany, Ma" uniqKey="Aleskandarany M">MA Aleskandarany</name></author><author><name sortKey="Rakha, Ea" uniqKey="Rakha E">EA Rakha</name></author><author><name sortKey="Ahmed, Ma" uniqKey="Ahmed M">MA Ahmed</name></author><author><name sortKey="Powe, Dg" uniqKey="Powe D">DG Powe</name></author><author><name sortKey="Paish, Ec" uniqKey="Paish E">EC Paish</name></author><author><name sortKey="Macmillan, Rd" uniqKey="Macmillan R">RD Macmillan</name></author><author><name sortKey="Ellis, Io" uniqKey="Ellis I">IO Ellis</name></author><author><name sortKey="Green, Ar" uniqKey="Green A">AR Green</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bachman, Ke" 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ref-type="aff" rid="aff65">65</xref></contrib><contrib contrib-type="author"><name><surname>Sangrajrang</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff66">66</xref></contrib><contrib contrib-type="author"><name><surname>Gabrieau</surname><given-names>V</given-names></name><xref ref-type="aff" rid="aff67">67</xref></contrib><contrib contrib-type="author"><name><surname>Brennan</surname><given-names>P</given-names></name><xref ref-type="aff" rid="aff67">67</xref></contrib><contrib contrib-type="author"><name><surname>McKay</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff67">67</xref></contrib><contrib contrib-type="author"><name><surname>Anton-Culver</surname><given-names>H</given-names></name><xref ref-type="aff" rid="aff68">68</xref></contrib><contrib contrib-type="author"><name><surname>Ziogas</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff68">68</xref></contrib><contrib contrib-type="author"><name><surname>Couch</surname><given-names>F J</given-names></name><xref ref-type="aff" rid="aff69">69</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><contrib contrib-type="author"><name><surname>Easton</surname><given-names>D F</given-names></name><xref ref-type="aff" rid="aff63">63</xref><xref ref-type="aff" rid="aff64">64</xref></contrib><contrib contrib-type="author"><collab>the <institution>GENICA Network, kConFab Investigators, Australian Ovarian Cancer Study Group</institution><xref ref-type="author-notes" rid="note1"><sup>70</sup></xref></collab></contrib><aff id="aff1"><label>1</label><institution>Department of Health Sciences Research, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></aff><aff id="aff2"><label>2</label><institution>Sections of Epidemiology and Genetics, Institute of Cancer Research and Breakthrough Breast Cancer Research Centre</institution>, 123 Old Brompton Road, London SW7 3RP,<country>UK</country></aff><aff id="aff3"><label>3</label><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></aff><aff id="aff4"><label>4</label><institution>Department of Pathology, The University of Melbourne</institution>, Victoria 3010,<country>Australia</country></aff><aff id="aff5"><label>5</label><institution>The Netherlands Cancer Institute</institution>, Plesmanlaan 121, 1066 CX, Amsterdam,<country>The Netherlands</country></aff><aff id="aff6"><label>6</label><institution>Leiden University Medical Center</institution>, Albinusdreef 2, 2333 ZA, Leiden,<country>The Netherlands</country></aff><aff id="aff7"><label>7</label><institution>Division of Hematology and Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine</institution>, Los Angeles, CA 90095,<country>USA</country></aff><aff id="aff8"><label>8</label><institution>Department of Gynecology and Obstetrics, University Breast Center Franconia, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></aff><aff id="aff9"><label>9</label><institution>Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg</institution>, Schloßplatz 4, 91054 Erlangen,<country>Germany</country></aff><aff id="aff10"><label>10</label><institution>Breakthrough Breast Cancer Research Centre, Institute of Cancer Research</institution>, 123 Old Brompton Road, London SW7 3RP,<country>UK</country></aff><aff id="aff11"><label>11</label><institution>Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine</institution>, Keppel Street, London WC1E 7HT,<country>UK</country></aff><aff id="aff12"><label>12</label><institution>National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust, Guy's Hospital</institution>, Great Maze Pond, London SE19RT,<country>UK</country></aff><aff id="aff13"><label>13</label><institution>Oxford Biomedical Research Centre, Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford</institution>, Oxford OX3 7BN,<country>UK</country></aff><aff id="aff14"><label>14</label><institution>NUIG Department of Surgery, Clinical Science Institute, University Hospital Galway</institution>, Galway 091 524 411,<country>Ireland</country></aff><aff id="aff15"><label>15</label><institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute</institution>, 6120 Executive Boulevard, MSC 7242, Bethesda, MD 20892-7335,<country>USA</country></aff><aff id="aff16"><label>16</label><institution>Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center, Institute of Oncology</institution>, 5 Roentgena Street, 02-781 Warsaw,<country>Poland</country></aff><aff id="aff17"><label>17</label><institution>Program in Molecular and Genetic Epidemiology, Harvard School of Public Health</institution>, 677 Huntington Avenue, Boston, MA 02115,<country>USA</country></aff><aff id="aff18"><label>18</label><institution>Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO)</institution>, Calle Melchor Fernández Almagro 3, Madrid 28029,<country>Spain</country></aff><aff id="aff19"><label>19</label><institution>Servicio de Cirugía General y Especialidades, Hospital Monte Naranco</institution>, Av. Doctores Fernández Vega 107, Oviedo 33012,<country>Spain</country></aff><aff id="aff20"><label>20</label><institution>Human Gentyping Unit (CeGen), Spanish National Cancer Research Centre (CNIO)</institution>, Madrid,<country>Spain</country></aff><aff id="aff21"><label>21</label><institution>Human Genetics Group, Spanish National Cancer Research Centre (CNIO)</institution>, Calle Melchor Fernández Almagro 3, Madrid 28029,<country>Spain</country></aff><aff id="aff22"><label>22</label><institution>Department of Obstetrics and Gynecology, University Hospital Heidelberg</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></aff><aff id="aff23"><label>23</label><institution>Molecular Epidemiology Group, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></aff><aff id="aff24"><label>24</label><institution>Department of Gynaecology and Obstetrics, Technical University of Munich</institution>, Arcisstraße 21, 80333 Munich,<country>Germany</country></aff><aff id="aff25"><label>25</label><institution>Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Center of Molecular Medicine Cologne (CMMC), University Hospital of Cologne</institution>, 50931 Cologne,<country>Germany</country></aff><aff id="aff26"><label>26</label><institution>Institute of Human Genetics, University of Heidelberg</institution>, Im Neuenheimer Feld 366, 69120 Heidelberg,<country>Germany</country></aff><aff id="aff27"><label>27</label><institution>Deutsches Krebsforschungszentrum (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></aff><aff id="aff28"><label>28</label><institution>Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Betriebsstätte Johanniter Krankenhaus</institution>, Johanniterstraße 3-5; 53113 Bonn,<country>Germany</country></aff><aff id="aff29"><label>29</label><institution>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA)</institution>, Burkle-de-la-Camp-Platz 1, 44789 Bochum,<country>Germany</country></aff><aff id="aff30"><label>30</label><institution>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)</institution>, Im Neuenheimer Feld 280, D-69120 Heidelberg,<country>Germany</country></aff><aff id="aff31"><label>31</label><institution>Department of Obstetrics and Gynecology, University of Ulm</institution>, Albert-Einstein-Allee 11, 89081 Ulm,<country>Germany</country></aff><aff id="aff32"><label>32</label><institution>Hannover Medical School, Gynaecology Research Unit</institution>, 30625 Hannover,<country>Germany</country></aff><aff id="aff33"><label>33</label><institution>Hannover Medical School, Clinics of Radiation Oncology</institution>, 30625 Hannover,<country>Germany</country></aff><aff id="aff34"><label>34</label><institution>Hannover Medical School, Clinics of Obstetrics and Gynaecology</institution>, 30625 Hannover,<country>Germany</country></aff><aff id="aff35"><label>35</label><institution>Department of Molecular Medicine and Surgery, Karolinska Institutet</institution>, S17176 Stockholm,<country>Sweden</country></aff><aff id="aff36"><label>36</label><institution>Department of Oncology Pathology, Karolinska Institutet</institution>, S17176 Stockholm,<country>Sweden</country></aff><aff id="aff37"><label>37</label><institution>Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland and Kuopio University Hospital</institution>, Biocenter Kuopio, FI-70211 Kuopio,<country>Finland</country></aff><aff id="aff38"><label>38</label><institution>Institute of Clinical Medicine, Department of Oncology, University of Eastern Finland, Kuopio University Hospital</institution>, FI-70211 Kuopio,<country>Finland</country></aff><aff id="aff39"><label>39</label><institution>Queensland Institute of Medical Research</institution>, 300 Herston Road, Herston, QLD 4029,<country>Australia</country></aff><aff id="aff40"><label>40</label><institution>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT) and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare</institution>; via Adamello, 16 - 20139 Milano,<country>Italy</country></aff><aff id="aff41"><label>41</label><institution>Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia</institution>, via Ripamonti 435, 20141 Milano,<country>Italy</country></aff><aff id="aff42"><label>42</label><institution>Department of Experimental Oncology, Istituto Europeo di Oncologia and Consortium for Genomics Technology (Cogentech)</institution>; via Adamello, 16 - 20139 Milano,<country>Italy</country></aff><aff id="aff43"><label>43</label><institution>Unit of Medical Genetics, Department of Preventive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT)</institution>, via Venezian 1 - 20133 Milano,<country>Italy</country></aff><aff id="aff44"><label>44</label><institution>Cancer Epidemiology Centre, Cancer Council Victoria</institution>, 1 Rathdowne Street, Carlton VIC 3053,<country>Australia</country></aff><aff id="aff45"><label>45</label><institution>Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne</institution>, Level 4, 207 Bouverie Street, Victoria 3010,<country>Australia</country></aff><aff id="aff46"><label>46</label><institution>Department of Anatomical Pathology, The Alfred Hospital</institution>, Commercial Road, Prahran VIC 3181,<country>Australia</country></aff><aff id="aff47"><label>47</label><institution>Department of Epidemiology, Cancer Prevention Institute of California</institution>, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538,<country>USA</country></aff><aff id="aff48"><label>48</label><institution>Department of Surgery, Dana-Farber Cancer Institute</institution>, 450 Brookline Avenue, Boston, MA 02215-5450,<country>USA</country></aff><aff id="aff49"><label>49</label><institution>Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></aff><aff id="aff50"><label>50</label><institution>Department of Oncology, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></aff><aff id="aff51"><label>51</label><institution>Department of Surgery, University of Oulu, Oulu University Hospital</institution>, Aapistie 5 A, 90220 Oulu,<country>Finland</country></aff><aff id="aff52"><label>52</label><institution>Ontario Cancer Genetics Network, Cancer Care Ontario</institution>, 620 University Avenue, Toronto, ON M5G 2C1 ON,<country>Canada</country></aff><aff id="aff53"><label>53</label><institution>Fred A. Litwin Center for Cancer Genetics, Mount Sinai Hospital</institution>, 600 University Avenue, Toronto, ON M5G 1X5, ON<country>Canada</country></aff><aff id="aff54"><label>54</label><institution>Department of Molecular Genetics, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></aff><aff id="aff55"><label>55</label><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, 600 University Avenue, Toronto, ON M5G 1X5 ON,<country>Canada</country></aff><aff id="aff56"><label>56</label><institution>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></aff><aff id="aff57"><label>57</label><institution>Department of Laboratory Medicine and Pathobiology, University of Toronto</institution>, 105 George Street, Toronto, ON M5A 2N4 ON,<country>Canada</country></aff><aff id="aff58"><label>58</label><institution>Department of Laboratory Medicine and Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital</institution>, 30 Bond Street, Toronto, ON M5B 1W8 ON,<country>Canada</country></aff><aff id="aff59"><label>59</label><institution>Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></aff><aff id="aff60"><label>60</label><institution>Medical Genetics Research Group, Faculty of Medicine and Human Sciences, University of Manchester</institution>, Oxford Road, Manchester M13 9PL,<country>UK</country></aff><aff id="aff61"><label>61</label><institution>Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield</institution>, Beech Hill Road, Sheffield S102RX,<country>UK</country></aff><aff id="aff62"><label>62</label><institution>United Kingdom Department of Oncology and Department of Public Health and Primary Care University of Cambridge</institution>, Cambridge,<country>UK</country></aff><aff id="aff63"><label>63</label><institution>Department of Oncology, University of Cambridge</institution>, Robinson Way, Cambridge CB2 0RE,<country>UK</country></aff><aff id="aff64"><label>64</label><institution>Centre for Cancer Genetic Epidemiology, University of Cambridge</institution>, Worts Causeway, Cambridge CB1 8RN,<country>UK</country></aff><aff id="aff65"><label>65</label><institution>Seoul National University College of Medicine</institution>, Yongon _103 Daehak-ro, Jongno-gu, Seoul 110-799,<country>Korea</country></aff><aff id="aff66"><label>66</label><institution>National Cancer Institute</institution>, Rama 6 Road, 10400 Bangkok,<country>Thailand</country></aff><aff id="aff67"><label>67</label><institution>International Agency for Research on Cancer</institution>, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08,<country>France</country></aff><aff id="aff68"><label>68</label><institution>Department of Epidemiology, School of Medicine, University of California Irvine</institution>, 224 Irvine Hall, Irvine, CA 92697,<country>USA</country></aff><aff id="aff69"><label>69</label><institution>Department of Laboratory Medicine and Pathology, Mayo Clinic</institution>, 200 First Street SW, Rochester, MN 55905,<country>USA</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label>E-mail: <email>couch.fergus@mayo.edu</email></corresp><fn fn-type="present-address" id="note1"><label>70</label><p>See <xref ref-type="app" rid="app1">Appendix</xref>.</p></fn></author-notes><pub-date pub-type="ppub"><day>06</day><month>12</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>27</day><month>10</month><year>2011</year></pub-date><volume>105</volume><issue>12</issue><fpage>1934</fpage><lpage>1939</lpage><history><date date-type="received"><day>12</day><month>07</month><year>2011</year></date><date date-type="rev-recd"><day>16</day><month>09</month><year>2011</year></date><date date-type="accepted"><day>28</day><month>09</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 Cancer Research UK</copyright-statement><copyright-year>2011</copyright-year><copyright-holder>Cancer Research UK</copyright-holder></permissions><abstract><sec><title>Background:</title><p>Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (<italic>PIK3CA</italic>) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.</p></sec><sec><title>Methods:</title><p>A single-nucleotide polymorphism from the <italic>PIK3CA</italic> locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).</p></sec><sec><title>Results:</title><p>Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95–0.99, <italic>P</italic>=4.6 × 10<sup>−3</sup>), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96–1.01, <italic>P</italic>=0.139).</p></sec><sec><title>Conclusion:</title><p>Common germline variation in <italic>PIK3CA</italic> does not have a strong influence on the risk of breast cancer</p></sec></abstract><kwd-group><kwd>genetic susceptibility</kwd><kwd>neoplasms</kwd><kwd>association study</kwd></kwd-group></article-meta></front><body><p>Phosphatidylinositol-3 kinases (PI3Ks) constitute a lipid kinase family integral to signalling pathways that regulate many cancer-related processes, including cell proliferation, adhesion, apoptosis, survival and motility (<xref ref-type="bibr" rid="bib6">Fruman <italic>et al</italic>, 1998</xref>; <xref ref-type="bibr" rid="bib4">Cantley, 2002</xref>). Alteration of PI3K family members, such as amplification of the phosphoinositide-3-kinase catalytic subunit alpha (<italic>PIK3CA</italic>) oncogene on chromosome 3q26 that encodes the p110<italic>α</italic> catalytic subunit of PI3K, are commonly observed in human cancers. Amplification and overexpression of <italic>PIK3CA</italic> results in increased production of the phosphatidylinositol-3,4,5-triphosphate second messenger, hyperactivation of the PI3K/AKT pathway, and stimulation of cellular transformation and tumour progression (<xref ref-type="bibr" rid="bib19">Shayesteh <italic>et al</italic>, 1999</xref>; <xref ref-type="bibr" rid="bib14">Ma <italic>et al</italic>, 2000</xref>; <xref ref-type="bibr" rid="bib5">Fresno Vara <italic>et al</italic>, 2004</xref>; <xref ref-type="bibr" rid="bib16">Saal <italic>et al</italic>, 2005</xref>; <xref ref-type="bibr" rid="bib17">Samuels and Ericson, 2006</xref>). Somatic mutations in <italic>PIK3CA</italic> are also common in colon (18–32%), gastric (4–25%), endometrial (36%), liver (36%), brain (27%) and breast (18–40%) tumours (<xref ref-type="bibr" rid="bib2">Bachman <italic>et al</italic>, 2004</xref>; <xref ref-type="bibr" rid="bib3">Campbell <italic>et al</italic>, 2004</xref>; <xref ref-type="bibr" rid="bib18">Samuels <italic>et al</italic>, 2004</xref>; <xref ref-type="bibr" rid="bib9">Karakas <italic>et al</italic>, 2006</xref>; <xref ref-type="bibr" rid="bib12">Ligresti <italic>et al</italic>, 2009</xref>). Functional analyses have shown that many of these mutations activate PIK3CA enzymatic activity and stimulate downstream AKT signalling, promoting growth factor-independent growth and metastasis (<xref ref-type="bibr" rid="bib18">Samuels <italic>et al</italic>, 2004</xref>; <xref ref-type="bibr" rid="bib17">Samuels and Ericson, 2006</xref>).</p><p>In breast tumours, <italic>PIK3CA</italic> mutations have been consistently associated with ER-positive and human epidermal growth factor receptor-2 (HER2)-positive tumour status (<xref ref-type="bibr" rid="bib16">Saal <italic>et al</italic>, 2005</xref>; <xref ref-type="bibr" rid="bib11">Li <italic>et al</italic>, 2006</xref>; <xref ref-type="bibr" rid="bib15">Perez-Tenorio <italic>et al</italic>, 2007</xref>; <xref ref-type="bibr" rid="bib20">Stemke-Hale <italic>et al</italic>, 2008</xref>) (<xref ref-type="bibr" rid="bib16">Saal <italic>et al</italic>, 2005</xref>; <xref ref-type="bibr" rid="bib15">Perez-Tenorio <italic>et al</italic>, 2007</xref>). The correlation between these mutations and breast cancer prognosis is less clear, with several studies reporting associations between <italic>PIK3CA</italic> mutations and lymph node metastasis and worse overall and breast cancer-specific survival (<xref ref-type="bibr" rid="bib16">Saal <italic>et al</italic>, 2005</xref>; <xref ref-type="bibr" rid="bib11">Li <italic>et al</italic>, 2006</xref>; <xref ref-type="bibr" rid="bib10">Lai <italic>et al</italic>, 2008</xref>; <xref ref-type="bibr" rid="bib1">Aleskandarany <italic>et al</italic>, 2010</xref>), whereas other studies have reported associations with longer survival particularly among patients with ER-positive, HER2-negative tumours (<xref ref-type="bibr" rid="bib15">Perez-Tenorio <italic>et al</italic>, 2007</xref>; <xref ref-type="bibr" rid="bib8">Kalinsky <italic>et al</italic>, 2009</xref>; <xref ref-type="bibr" rid="bib13">Loi <italic>et al</italic>, 2010</xref>).</p><p>Although the pathological and clinical significance of <italic>PIK3CA</italic> somatic mutations has been well studied, the contribution of inherited variation in this important oncogene to risk of breast cancer is unknown. Here we investigated the influence of germline variation in <italic>PIK3CA</italic> on breast cancer risk.</p><sec sec-type="materials|methods"><title>Materials and Methods</title><sec><title>Mayo clinic breast cancer study</title><p>The details of the Mayo Clinic Breast Cancer case–control Study (MCBCS) have been described previously (<xref ref-type="bibr" rid="bib22">Wang <italic>et al</italic>, 2008</xref>). Briefly, cases were comprised of Caucasian women with invasive breast cancer diagnosed within 6 months of ascertainment with no prior history of cancer. Controls were comprised of Caucasian women visiting the Mayo Clinic for general medical exams in the Department of Internal Medicine with no prior history of cancer. Participants were recruited under an Institutional Review Board approved protocol. A total of 798 cases and 843 controls were utilised for stage 1 genotyping (<xref rid="tbl1" ref-type="table">Table 1</xref>).</p></sec><sec><title>Replication studies</title><p>The Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer case–control study and 26 case–control studies from Breast Cancer Association Consortium (BCAC) contributed data to these analyses (described in <xref ref-type="supplementary-material" rid="sup1">Supplementary Table 1</xref>). Stage 1 of the CGEMS GWAS included 1145 cases and 1142 controls of self-reported white European ancestry (<xref ref-type="bibr" rid="bib21">Thomas <italic>et al</italic>, 2009</xref>), whereas the combined Stage 1 and 2 of CGEMS included a total of 5436 cases and 5280 controls (<xref rid="tbl1" ref-type="table">Table 1</xref>). The BCAC replication was comprised of 24 studies of women of primarily European descent (<xref ref-type="supplementary-material" rid="sup1">Supplementary Table 1</xref>), 1702 additional samples from MCBCS and two studies (SEBCS and TBCS) of women from Southeast Asia (<xref rid="tbl1" ref-type="table">Table 1</xref>). Final combined analyses included 35 991 breast cancer cases and 35 153 controls of white European ancestry, as well as 2183 breast cancer cases and 1469 controls of Asian ancestry. Study participants were recruited under protocols approved by the institutional review board at each institution and all subjects provided written informed consent.</p></sec><sec><title>Genotyping</title><p>Four haplotype-tagging single-nucleotide polymorphisms (SNPs) within <italic>PIK3CA</italic> (rs13320527, rs3729692, rs1607237, rs9838117) were selected (<italic>r</italic><sup>2</sup>>0.80 in European–American genotype data from HapMap release 21). A total of 1741 Mayo Clinic samples (798 cases, 843 controls and 100 duplicates) were genotyped on custom oligo pool assays at Illumina Corporation (San Diego, CA, USA) using the Illumina GoldenGate assay. All SNPs had genotype call rates >95%. Concordance between duplicate samples was 100%. Genotyping of rs1607237 in CGEMS and BCAC was performed using a TaqMan allelic discrimination assay or the Sequenom platform (Sequenom, San Diego, CA, USA) via standard protocols. Genotyping concordance was verified with internal duplicates and overall data quality was ensured using independent genotyping of 96 CEU samples by each genotyping center (<xref ref-type="bibr" rid="bib7">Garcia-Closas <italic>et al</italic>, 2008</xref>). All studies met the specified criteria for call rate (>95%).</p></sec><sec><title>Pathology and tumour markers</title><p>The collection of pathology and tumour marker information for BCAC has been described previously (<xref ref-type="bibr" rid="bib23">Yang <italic>et al</italic>, 2011</xref>). Pathology data were also available for 900 CGEMS subjects. Briefly, studies provided information on histopathological subtype, grade of differentiation, tumour size, nodal involvement and stage at diagnosis of breast tumours. All studies except BBCS, GC-HBOC and HMBCS provided data on ER and progesterone receptor (PR) status of tumours, and 12 studies provided data on HER2 (<xref ref-type="supplementary-material" rid="sup1">Supplementary Table 2</xref>). ER/PR status was most commonly defined using data from medical records. Oestrogen receptor and PR negative status was defined as <10% of the tumour cells stained. Human epidermal growth factor receptor-2-negative status was typically defined as a score of 0 or 1+ on a HER2 immunohistochemistry (IHC) scale of 0–3+.</p></sec><sec><title>Statistical methods</title><p>Evidence of departure from Hardy–Weinberg equilibrium (HWE) was assessed in controls using a goodness of fit test and none was observed (HWE <italic>P</italic>⩾0.001). Single-nucleotide polymorphism associations were tested using unconditional logistic regression adjusting for age and state of residence in a log-additive model. We also calculated odds ratios (ORs) and 95% confidence intervals (CIs) separately for heterozygotes and rare homozygotes. The association between rs1607237 and breast cancer risk in stage 1 of the CGEMS GWAS was evaluated as previously described (<xref ref-type="bibr" rid="bib21">Thomas <italic>et al</italic>, 2009</xref>). Associations with breast cancer risk in the BCAC studies and the combined BCAC, MCBCS and CGEMS studies were evaluated using unconditional logistic regression adjusting for study center. A likelihood ratio test of heterogeneity by age groups was not significant (<italic>P</italic>=0.10), and further adjustment for age did not change the results. Analyses of pathology-specific subsets of cases were conducted using polytomous regression with controls as the reference outcome, adjusting for study site.</p></sec></sec><sec><title>Results</title><p>Of four <italic>PIK3CA</italic> haplotype-tagging SNPs, rs1607237 was significantly associated with risk of breast cancer in MCBCS (OR=0.85, 95% CI 0.73–0.98, <italic>P</italic>=0.023; <xref rid="tbl2" ref-type="table">Table 2</xref>, <xref ref-type="supplementary-material" rid="sup1">Supplementary Figure 1</xref>). Next we evaluated associations between rs1607237 and breast cancer risk in 1145 cases and 1142 controls genotyped in stage 1 of the CGEMS breast cancer GWAS (<xref ref-type="bibr" rid="bib21">Thomas <italic>et al</italic>, 2009</xref>). Rs1607237 was significantly associated with breast cancer risk (heterozygous OR=1.12, homozygous OR=0.79, score <italic>P</italic>=0.017). To provide a more stable estimate of risk in this population, 8429 additional CGEMS subjects were genotyped for rs1607237. In all 5436 cases and 5280 controls from stage 1 and 2 of CGEMS, rs1607237 was strongly associated with a decrease in breast cancer risk (OR=0.92, 95% CI 0.88–0.98, <italic>P</italic>=0.0050; <xref rid="tbl2" ref-type="table">Table 2</xref>).</p><p>This finding provided the rationale for further evaluation of this SNP in 23 BCAC studies involving women of European ancestry (28 766 cases, 28 319 controls), and two BCAC studies of Asian women (2183 cases, 1469 controls; <xref rid="tbl1" ref-type="table">Table 1</xref>). Rs1607237 was not significantly associated with breast cancer risk in the 23 BCAC studies of women of European ancestry (OR=0.98, 95% CI 0.96–1.01, <italic>P</italic>=0.139) or in the two Asian BCAC studies (OR=1.05, 95% CI 0.94–1.16, <italic>P</italic>=0.39; <xref rid="tbl2" ref-type="table">Table 2</xref>). However, when combining all genotype data from the three stages of this study (MCBCS, CGEMS and BCAC; <xref ref-type="supplementary-material" rid="sup1">Supplementary Table 3</xref>), rs1607237 was significantly associated with risk of breast cancer (OR=0.97, 95% CI 0.95–0.99, <italic>P</italic>=9.5 × 10<sup>−3</sup>). Similarly, a significant association was observed when considering only women of European ancestry in the combined analysis (OR=0.97, 95% CI 0.95–0.99, <italic>P</italic>=4.6 × 10<sup>−3</sup>; (<xref rid="tbl2" ref-type="table">Table 2</xref>). There was no evidence of heterogeneity by study site among the 25 Caucasian studies (<italic>P</italic>=0.14; <xref ref-type="supplementary-material" rid="sup1">Supplementary Figure 2</xref>).</p><p>To further understand the association with breast cancer, we restricted the analysis to women with invasive breast cancer. Rs1607237 was associated with a reduced risk of invasive breast cancer (OR=0.97, 95% CI 0.95–0.99, <italic>P</italic>=0.012; <xref rid="tbl2" ref-type="table">Table 2</xref>), whereas no association with risk of ductal carcinoma <italic>in situ</italic> was observed (OR=0.93, 95% CI 0.85–1.02, <italic>P</italic>=0.12). In addition, we explored differences in <italic>PIK3CA</italic> SNP associations in the combined data set by tumour subtype (<xref ref-type="supplementary-material" rid="sup1">Supplementary Table 4</xref>). The rs1607237 variant was not associated with any subtypes defined by ER, PR or HER2 status, although it is important to note the reduction in sample size when restricting to these tumour subtypes.</p></sec><sec><title>Discussion</title><p>Here we report an association between inherited variation in the oncogene <italic>PIK3CA</italic> and risk of breast cancer in a large, three-stage analysis utilising nearly 75 000 subjects from 27 case–control study studies. We show that rs1607237 is significantly associated with a small decrease in breast cancer risk (OR=0.97, 95% CI 0.95–0.99, <italic>P</italic>=9.5 × 10<sup>−3</sup>) in all studies combined and when considering only women of European ancestry in the combined studies (OR=0.97, 95% CI 0.95–0.99, <italic>P</italic>=4.6 × 10<sup>−3</sup>). However, the association did not achieve significance in the large third stage involving only BCAC studies. Although the first two stages of our analysis suggest an association between <italic>PIK3CA</italic> and breast cancer risk, our inability to confirm this finding in the BCAC studies suggests that the result should be interpreted with caution.</p><p>We further explored the linkage disequilibrium patterns in the <italic>PIK3CA</italic> coding and promoter regions to better understand the relationship between rs1607237 and other variation in this region. Rs1607237 was not in strong linkage disequilibrium with two non-synonymous polymorphic variants in the coding region of <italic>PIK3CA</italic>, rs1051399 (<italic>r</italic><sup>2</sup>=0.0060) and rs3729680 (<italic>r</italic><sup>2</sup>=0.034), which had been genotyped in HapMap samples of European ancestry. However, an additional 18 non-synonymous variants were either not polymorphic or had not been genotyped in the HapMap samples, making inference about the relationship between rs1607237 and all variants of unknown significance in the <italic>PIK3CA</italic> coding region difficult. In addition, two <italic>PIK3CA</italic> promoter SNPs were in low LD with rs1607237 (rs9831234, <italic>r</italic><sup>2</sup>=0.16; rs2865084, <italic>r</italic><sup>2</sup>=0.038). However, it remains possible that <italic>PIK3CA</italic> promoter SNPs that were not captured in this study are related to breast cancer risk.</p><p>It is also important to note that the effect estimate for rs1607237 in the BCAC replication studies and in the overall BCAC, MCBCS and CGEMS studies is quite small (OR=0.97). This limits our statistical power to detect significant associations in these studies despite the large sample size, particularly in analyses utilising pathology information that is available for only a subset of subjects. Similarly, we had limited power to detect associations in the original MCBCS study with the three non-significant <italic>PIK3CA</italic> SNPs. Thus, it remains possible that evaluation of these variants in the larger BCAC cohort might detect associations with risk. While the effect of rs1607237 on risk is small, the association between inherited variation in this important oncogene and breast cancer risk does provide valuable biological insight into the development of this disease. Validation of rs1607237 in GWAS studies from other large collaborative groups and additional studies by BCAC with detailed pathology information are necessary to confirm this association. Functional evaluation of this variant is needed to fully understand the relationship between inherited <italic>PIK3CA</italic> variation and breast cancer risk.</p></sec></body><back><ack><p>The ABCS study was funded by the Dutch Cancer Society (grants NKI 2001-2423; NKI 2007-3839), the Dutch National Genomics Initiative; ABCS acknowledges all patients, and Sten Cornelissen, Richard van Hien, Flora van Leeuwen, Vincent Smit and other contributors to the ‘BOSOM' study (ABCS). The ABCFS, NC-BCFR and OFBCR works were supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organisations imply endorsement by the US 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. JLH is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. MCS is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. BBCC is funded in part by the ELAN fund of the University Hospital 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). ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI081583 and PI081120). We thank Charo Alonso, Tais Moreno, Guillermo Pita, Primitiva Menéndez and Pilar Zamora for their contribution to this work. The GC-HBOC was collected within a project funded by the Deutsche Krebshilfe (Grant number: 107054). It was supported by the Dietmar-Hopp Foundation, the Helmholtz society and the German Cancer Research Center (DKFZ). We thank Sandrine Tchatchou for genotyping. The HABCS was supported by an intramural grant from Hannover Medical School. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to NB), and the Friends of Hannover Medical School (to NB). KARBAC acknowledges The Swedish Cancer Society and The Stockholm Cancer Society. KBCP is supported by grants from the Finnish Cancer Society; the Academy of Finland (grant number 127220); the special Government Funding (EVO) of Kuopio University Hospital (grant number 5654113 and 5501) and by the strategic funding of the University of Eastern Finland. We thank Mrs Helena Kemiläinen, Mrs Aija Parkkinen and Mrs Eija Myöhänen for their skillful technical assistance. We 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 (funded 2001–2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729); the Cancer Council of Tasmania and Cancer Foundation of Western Australia; and the NHMRC [199600]. GC-T is supported by the NHMRC. PP is supported by funds from Italian citizens who allocated the 5 × 1000 share of their tax payment to the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000'). MBCSG thanks Paolo Radice, Bernard Peissel, Daniela Zaffaroni and Marco A Pierotti of the Fondazione IRCCS Istituto Nazionale Tumori and Monica Barile of the Istituto Europeo di Oncologia, Milano, Italy. MCBCS was supported by NIH grant CA122340 and US Recovery act award CA122340Z. Many people have contributed to the MCCS, including the original investigators and the diligent teams who recruited the participants and who continue working on follow-up. Finally, we express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. Cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu and the Oulu University Hospital. SBCS was funded by the Breast Cancer Campaign and Yorkshire Cancer Research. The authors acknowledge Helen Cramp, Sue Higham, Dan Connley, Saba Balasubramanian. The UCIBCS is supported by the National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420.</p></ack><app-group><app id="app1"><title>APPENDIX</title><sec><title>The GENICA Network</title><p>Gene Environment Interaction and Breast Cancer in Germany (GENICA): Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University Tübingen, Germany (Hiltrud Brauch, Christina Justenhoven); Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany (UH); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (YDK, Christian Baisch); Institute of Pathology, Medical Faculty of the University of Bonn, Germany (Hans-Peter Fischer); Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany (TB, Beate Pesch, Volker Harth, Sylvia Rabstein). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.</p><p><italic>kConFab Investigators, Australian Ovarian Cancer Study Group</italic></p><p>Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne VIC 3002, Australia.</p></sec></app></app-group><fn-group><fn><p><xref ref-type="supplementary-material" rid="sup1">Supplementary Information</xref> accompanies the paper on British Journal of Cancer website (http://www.nature.com/bjc)</p></fn><fn><p>This work is published under the standard license to publish agreement. 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content-type="local-data" id="xob3"><label>Supplementary Figure Legends</label><media mimetype="application" mime-subtype="msword" xlink:href="bjc2011448x3.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="xob4"><label>Supplementary Tables</label><media mimetype="application" mime-subtype="msword" xlink:href="bjc2011448x4.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></sec></back><floats-group><table-wrap id="tbl1"><label>Table 1</label><caption><title>Studies contributing to evaluation of associations between rs1607237 and breast cancer risk</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Study</bold><xref ref-type="fn" rid="t1-fn1">a</xref></th><th align="left" valign="top" charoff="50"><bold>Country</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Cases <italic>n</italic> (%)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Controls <italic>n</italic> (%)</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">ABCFS</td><td align="left" valign="top" charoff="50">Australia</td><td align="char" valign="top" char="(" charoff="50">1199 (3.1)</td><td align="char" valign="top" char="(" charoff="50">438 (1.2)</td></tr><tr><td align="left" valign="top" charoff="50">ABCS</td><td align="left" valign="top" charoff="50">The Netherlands</td><td align="char" valign="top" char="(" charoff="50">1465 (3.8)</td><td align="char" valign="top" char="(" charoff="50">548 (1.5)</td></tr><tr><td align="left" valign="top" charoff="50">BBCC</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="(" charoff="50">1060 (2.8)</td><td align="char" valign="top" char="(" charoff="50">994 (2.7)</td></tr><tr><td align="left" valign="top" charoff="50">BBCS</td><td align="left" valign="top" charoff="50">UK</td><td align="char" valign="top" char="(" charoff="50">1153 (3.0)</td><td align="char" valign="top" char="(" charoff="50">831 (2.3)</td></tr><tr><td align="left" valign="top" charoff="50">BIGGS</td><td align="left" valign="top" charoff="50">Ireland</td><td align="char" valign="top" char="(" charoff="50">1060 (2.8)</td><td align="char" valign="top" char="(" charoff="50">900 (2.5)</td></tr><tr><td align="left" valign="top" charoff="50">CGEMS<xref ref-type="fn" rid="t1-fn2">b</xref></td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="(" charoff="50">5436 (14.2)</td><td align="char" valign="top" char="(" charoff="50">5280 (14.4)</td></tr><tr><td align="left" valign="top" charoff="50">CNIO-BCS</td><td align="left" valign="top" charoff="50">Spain</td><td align="char" valign="top" char="(" charoff="50">752 (2.0)</td><td align="char" valign="top" char="(" charoff="50">823 (2.2)</td></tr><tr><td align="left" valign="top" charoff="50">GC-HBOC</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="(" charoff="50">864 (2.3)</td><td align="char" valign="top" char="(" charoff="50">1224 (3.3)</td></tr><tr><td align="left" valign="top" charoff="50">GENICA</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="(" charoff="50">1013 (2.7)</td><td align="char" valign="top" char="(" charoff="50">1012 (2.8)</td></tr><tr><td align="left" valign="top" charoff="50">GESBC</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="(" charoff="50">563 (1.5)</td><td align="char" valign="top" char="(" charoff="50">564 (1.5)</td></tr><tr><td align="left" valign="top" charoff="50">HABCS</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="(" charoff="50">1046 (2.7)</td><td align="char" valign="top" char="(" charoff="50">998 (2.7)</td></tr><tr><td align="left" valign="top" charoff="50">HMBCS</td><td align="left" valign="top" charoff="50">Belarus</td><td align="char" valign="top" char="(" charoff="50">1760 (4.6)</td><td align="char" valign="top" char="(" charoff="50">1015 (2.8)</td></tr><tr><td align="left" valign="top" charoff="50">KARBAC</td><td align="left" valign="top" charoff="50">Sweden</td><td align="char" valign="top" char="(" charoff="50">812 (2.1)</td><td align="char" valign="top" char="(" charoff="50">863 (2.4)</td></tr><tr><td align="left" valign="top" charoff="50">kConFab/AOCS</td><td align="left" valign="top" charoff="50">Australia/New Zealand</td><td align="char" valign="top" char="(" charoff="50">566 (1.5)</td><td align="char" valign="top" char="(" charoff="50">899 (2.5)</td></tr><tr><td align="left" valign="top" charoff="50">KBCP</td><td align="left" valign="top" charoff="50">Finland</td><td align="char" valign="top" char="(" charoff="50">485 (1.3)</td><td align="char" valign="top" char="(" charoff="50">427 (1.2)</td></tr><tr><td align="left" valign="top" charoff="50">MARIE</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="(" charoff="50">2754 (7.2)</td><td align="char" valign="top" char="(" charoff="50">5302 (14.5)</td></tr><tr><td align="left" valign="top" charoff="50">MBCSG</td><td align="left" valign="top" charoff="50">Italy</td><td align="char" valign="top" char="(" charoff="50">739 (1.9)</td><td align="char" valign="top" char="(" charoff="50">1231 (3.4)</td></tr><tr><td align="left" valign="top" charoff="50">MCBCS<xref ref-type="fn" rid="t1-fn3">c</xref></td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="(" charoff="50">1789 (4.7)</td><td align="char" valign="top" char="(" charoff="50">1554 (4.2)</td></tr><tr><td align="left" valign="top" charoff="50">MCCS</td><td align="left" valign="top" charoff="50">Australia</td><td align="char" valign="top" char="(" charoff="50">679 (1.8)</td><td align="char" valign="top" char="(" charoff="50">751 (2.1)</td></tr><tr><td align="left" valign="top" charoff="50">NC-BCFR</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="(" charoff="50">388 (1.0)</td><td align="char" valign="top" char="(" charoff="50">154 (0.4)</td></tr><tr><td align="left" valign="top" charoff="50">OBCS</td><td align="left" valign="top" charoff="50">Finland</td><td align="char" valign="top" char="(" charoff="50">544 (1.4)</td><td align="char" valign="top" char="(" charoff="50">509 (1.4)</td></tr><tr><td align="left" valign="top" charoff="50">OFBCR</td><td align="left" valign="top" charoff="50">Canada</td><td align="char" valign="top" char="(" charoff="50">1170 (3.1)</td><td align="char" valign="top" char="(" charoff="50">329 (0.9)</td></tr><tr><td align="left" valign="top" charoff="50">SBCS</td><td align="left" valign="top" charoff="50">UK</td><td align="char" valign="top" char="(" charoff="50">1217 (3.2)</td><td align="char" valign="top" char="(" charoff="50">1201 (3.3)</td></tr><tr><td align="left" valign="top" charoff="50">SEARCH</td><td align="left" valign="top" charoff="50">UK</td><td align="char" valign="top" char="(" charoff="50">6520 (17.1)</td><td align="char" valign="top" char="(" charoff="50">6779 (18.5)</td></tr><tr><td align="left" valign="top" charoff="50">SEBCS<xref ref-type="fn" rid="t1-fn4">d</xref></td><td align="left" valign="top" charoff="50">Korea</td><td align="char" valign="top" char="(" charoff="50">1732 (4.5)</td><td align="char" valign="top" char="(" charoff="50">1178 (3.2)</td></tr><tr><td align="left" valign="top" charoff="50">TBCS<xref ref-type="fn" rid="t1-fn4">d</xref></td><td align="left" valign="top" charoff="50">Thailand</td><td align="char" valign="top" char="(" charoff="50">451 (1.2)</td><td align="char" valign="top" char="(" charoff="50">291 (0.8)</td></tr><tr><td align="left" valign="top" charoff="50">UCIBCS</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="(" charoff="50">957 (2.5)</td><td align="char" valign="top" char="(" charoff="50">527 (1.4)</td></tr><tr><td align="left" valign="top" charoff="50">Total</td><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">38 174 (100)</td><td align="char" valign="top" char="(" charoff="50">36 622 (100)</td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><label>a</label><p>See <xref ref-type="supplementary-material" rid="sup1">Supplementary Table 1</xref> for definition of study acronyms.</p></fn><fn id="t1-fn2"><label>b</label><p>Stage 2: Cancer Genetic Markers of Susceptibility study.</p></fn><fn id="t1-fn3"><label>c</label><p>Includes Stage 1: Mayo Clinic Breast Cancer Study.</p></fn><fn id="t1-fn4"><label>d</label><p>Asian case–control studies.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl2"><label>Table 2</label><caption><title>Associations between rs1607237 and breast cancer in MCBCS, CGEMS and BCAC</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="("></col><col align="char" char="."></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="char" valign="top" char="(" charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th colspan="2" align="center" valign="top" char="(" charoff="50"><bold>2-d.f. model</bold><hr></hr></th></tr><tr><th align="left" valign="top" charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th colspan="2" align="center" valign="top" char="(" charoff="50"><bold>Log-additive model</bold><hr></hr></th><th align="center" valign="top" char="(" charoff="50"><bold>Heterozygous</bold><hr></hr></th><th align="center" valign="top" char="(" charoff="50"><bold>Homozygous</bold><hr></hr></th></tr><tr><th align="left" valign="top" charoff="50"> </th><th align="center" valign="top" char="." charoff="50"><bold>Cases</bold></th><th align="center" valign="top" char="." charoff="50"><bold>Controls</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th><th align="center" valign="top" char="." charoff="50"><bold><italic>P</italic>-value</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Stage 1: MCBCS</td><td align="char" valign="top" char="." charoff="50">798</td><td align="char" valign="top" char="." charoff="50">843</td><td align="char" valign="top" char="(" charoff="50">0.85 (0.73–0.98)</td><td align="char" valign="top" char="." charoff="50">0.023</td><td align="char" valign="top" char="(" charoff="50">0.75 (0.60–0.93)</td><td align="char" valign="top" char="(" charoff="50">0.76 (0.57–1.01)</td></tr><tr><td align="left" valign="top" charoff="50">Stage 2: CGEMS</td><td align="char" valign="top" char="." charoff="50">5436</td><td align="char" valign="top" char="." charoff="50">5280</td><td align="char" valign="top" char="(" charoff="50">0.92 (0.88–0.98)</td><td align="char" valign="top" char="." charoff="50">0.0050</td><td align="char" valign="top" char="(" charoff="50">1.00 (0.92–1.09)</td><td align="char" valign="top" char="(" charoff="50">0.82 (0.73–0.92)</td></tr><tr><td align="left" valign="top" charoff="50">Stage 3: BCAC</td><td align="char" valign="top" char="." charoff="50">28 766</td><td align="char" valign="top" char="." charoff="50">28 319</td><td align="char" valign="top" char="(" charoff="50">0.98 (0.96–1.01)</td><td align="char" valign="top" char="." charoff="50">0.139</td><td align="char" valign="top" char="(" charoff="50">0.96 (0.93–1.00)</td><td align="char" valign="top" char="(" charoff="50">0.97 (0.92–1.02)</td></tr><tr><td align="left" valign="top" charoff="50">Combined analysis</td><td align="char" valign="top" char="." charoff="50">35 991</td><td align="char" valign="top" char="." charoff="50">35 153</td><td align="char" valign="top" char="(" charoff="50">0.97 (0.95–0.99)</td><td align="char" valign="top" char="." charoff="50">0.0046</td><td align="char" valign="top" char="(" charoff="50">0.97 (0.93–1.00)</td><td align="char" valign="top" char="(" charoff="50">0.94 (0.90–0.98)</td></tr><tr><td align="left" valign="top" charoff="50">Invasive</td><td align="char" valign="top" char="." charoff="50">33 660</td><td align="char" valign="top" char="." charoff="50">34 988</td><td align="char" valign="top" char="(" charoff="50">0.97 (0.95–0.99)</td><td align="char" valign="top" char="." charoff="50">0.012</td><td align="char" valign="top" char="(" charoff="50">0.97 (0.94–1.00)</td><td align="char" valign="top" char="(" charoff="50">0.95 (0.90–0.99)</td></tr><tr><td align="left" valign="top" charoff="50">DCIS</td><td align="char" valign="top" char="." charoff="50">1159</td><td align="char" valign="top" char="." charoff="50">16 889</td><td align="char" valign="top" char="(" charoff="50">0.93 (0.85–1.02)</td><td align="char" valign="top" char="." charoff="50">0.12</td><td align="char" valign="top" char="(" charoff="50">0.98 (0.85–1.12)</td><td align="char" valign="top" char="(" charoff="50">0.84 (0.70–1.02)</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>Abbreviations: BCAC=Breast Cancer Association Consortium; CGEMS=Cancer Genetic Markers of Susceptibility; CI=confidence interval; DCIS=ductal carcinoma <italic>in situ</italic>; MCBCS=Mayo Clinic breast cancer case–control study; OR=odds ratio.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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