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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Common variants at 12p11, 12q24, 9p21, 9q31.2 and in <italic>ZNF365 </italic>are associated with breast cancer risk for <italic>BRCA1 </italic>and/or <italic>BRCA2 </italic>mutation carriers</title><author><name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C" last="Antoniou">Antonis C. Antoniou</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Kuchenbaecker, Karoline B" sort="Kuchenbaecker, Karoline B" uniqKey="Kuchenbaecker K" first="Karoline B" last="Kuchenbaecker">Karoline B. Kuchenbaecker</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Soucy, Penny" sort="Soucy, Penny" uniqKey="Soucy P" first="Penny" last="Soucy">Penny Soucy</name><affiliation><nlm:aff id="I2">Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, T3-57, Quebec City, QC Canada</nlm:aff></affiliation></author><author><name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Chen, Xiaoqing" sort="Chen, Xiaoqing" uniqKey="Chen X" first="Xiaoqing" last="Chen">Xiaoqing Chen</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcguffog, Lesley" sort="Mcguffog, Lesley" uniqKey="Mcguffog L" first="Lesley" last="Mcguffog">Lesley Mcguffog</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Lee, Andrew" sort="Lee, Andrew" uniqKey="Lee A" first="Andrew" last="Lee">Andrew Lee</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Barrowdale, Daniel" sort="Barrowdale, Daniel" uniqKey="Barrowdale D" first="Daniel" last="Barrowdale">Daniel Barrowdale</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Sinilnikova, Olga M" sort="Sinilnikova, Olga M" uniqKey="Sinilnikova O" first="Olga M" last="Sinilnikova">Olga M. Sinilnikova</name><affiliation><nlm:aff id="I4">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, 28 rue Laënnec, Lyon 69373, France and INSERM U1052, CNRS UMR5286, Université Lyon 1, Cancer Research Center of Lyon, 28 rue Laënnec, Lyon 69373, France</nlm:aff></affiliation></author><author><name sortKey="Caligo, Maria A" sort="Caligo, Maria A" uniqKey="Caligo M" first="Maria A" last="Caligo">Maria A. Caligo</name><affiliation><nlm:aff id="I5">Section of Genetic Oncology, Dept. of Laboratory Medicine, University and University Hospital of Pisa, Via Roma 57, 56125 Pisa, Italy</nlm:aff></affiliation></author><author><name sortKey="Loman, Niklas" sort="Loman, Niklas" uniqKey="Loman N" first="Niklas" last="Loman">Niklas Loman</name><affiliation><nlm:aff id="I6">Department of Oncology, Lund University Hospital, Lund, Sweden</nlm:aff></affiliation></author><author><name sortKey="Harbst, Katja" sort="Harbst, Katja" uniqKey="Harbst K" first="Katja" last="Harbst">Katja Harbst</name><affiliation><nlm:aff id="I6">Department of Oncology, Lund University Hospital, Lund, Sweden</nlm:aff></affiliation></author><author><name sortKey="Lindblom, Annika" sort="Lindblom, Annika" uniqKey="Lindblom A" first="Annika" last="Lindblom">Annika Lindblom</name><affiliation><nlm:aff id="I7">Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Arver, Brita" sort="Arver, Brita" uniqKey="Arver B" first="Brita" last="Arver">Brita Arver</name><affiliation><nlm:aff id="I8">Department of Oncology, Karolinska University Hospital, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rosenquist, Richard" sort="Rosenquist, Richard" uniqKey="Rosenquist R" first="Richard" last="Rosenquist">Richard Rosenquist</name><affiliation><nlm:aff id="I9">Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Karlsson, Per" sort="Karlsson, Per" uniqKey="Karlsson P" first="Per" last="Karlsson">Per Karlsson</name><affiliation><nlm:aff id="I10">Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Nathanson, Kate" sort="Nathanson, Kate" uniqKey="Nathanson K" first="Kate" last="Nathanson">Kate Nathanson</name><affiliation><nlm:aff id="I11">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Domchek, Susan" sort="Domchek, Susan" uniqKey="Domchek S" first="Susan" last="Domchek">Susan Domchek</name><affiliation><nlm:aff id="I11">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Rebbeck, Tim" sort="Rebbeck, Tim" uniqKey="Rebbeck T" first="Tim" last="Rebbeck">Tim Rebbeck</name><affiliation><nlm:aff id="I11">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Jakubowska, Anna" sort="Jakubowska, Anna" uniqKey="Jakubowska A" first="Anna" last="Jakubowska">Anna Jakubowska</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Lubinski, Jan" sort="Lubinski, Jan" uniqKey="Lubinski J" first="Jan" last="Lubinski">Jan Lubinski</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Jaworska, Katarzyna" sort="Jaworska, Katarzyna" uniqKey="Jaworska K" first="Katarzyna" last="Jaworska">Katarzyna Jaworska</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Durda, Katarzyna" sort="Durda, Katarzyna" uniqKey="Durda K" first="Katarzyna" last="Durda">Katarzyna Durda</name><affiliation><nlm:aff id="I13">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin and Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland</nlm:aff></affiliation></author><author><name sortKey="Zlowowcka Perlowska, El Bieta" sort="Zlowowcka Perlowska, El Bieta" uniqKey="Zlowowcka Perlowska E" first="El Bieta" last="Złowowcka-Perłowska">El Bieta Złowowcka-Perłowska</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Osorio, Ana" sort="Osorio, Ana" uniqKey="Osorio A" first="Ana" last="Osorio">Ana Osorio</name><affiliation><nlm:aff id="I14">Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain and Spanish Network on Rare Diseases (CIBERER)</nlm:aff></affiliation></author><author><name sortKey="Duran, Mercedes" sort="Duran, Mercedes" uniqKey="Duran M" first="Mercedes" last="Durán">Mercedes Durán</name><affiliation><nlm:aff id="I15">Institute of Biology and Molecular Genetics. Universidad de Valladolid (IBGM-UVA), Valladolid, Spain</nlm:aff></affiliation></author><author><name sortKey="Andres, Raquel" sort="Andres, Raquel" uniqKey="Andres R" first="Raquel" last="Andrés">Raquel Andrés</name><affiliation><nlm:aff id="I16">Oncology unit. Hospital clinico Universitario "Lozano Blesa", Zaragoza, Spain</nlm:aff></affiliation></author><author><name sortKey="Benitez, Javier" sort="Benitez, Javier" uniqKey="Benitez J" first="Javier" last="Benítez">Javier Benítez</name><affiliation><nlm:aff id="I17">Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain and Spanish Network on Rare Diseases (CIBERER)</nlm:aff></affiliation></author><author><name sortKey="Hamann, Ute" sort="Hamann, Ute" uniqKey="Hamann U" first="Ute" last="Hamann">Ute Hamann</name><affiliation><nlm:aff id="I18">Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Hogervorst, Frans B" sort="Hogervorst, Frans B" uniqKey="Hogervorst F" first="Frans B" last="Hogervorst">Frans B. Hogervorst</name><affiliation><nlm:aff id="I19">Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Os, Theo A" sort="Van Os, Theo A" uniqKey="Van Os T" first="Theo A" last="Van Os">Theo A. Van Os</name><affiliation><nlm:aff id="I20">Department of Clinical Genetics, Academic Meical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Verhoef, Senno" sort="Verhoef, Senno" uniqKey="Verhoef S" first="Senno" last="Verhoef">Senno Verhoef</name><affiliation><nlm:aff id="I21">Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Meijers Heijboer, Hanne Ej" sort="Meijers Heijboer, Hanne Ej" uniqKey="Meijers Heijboer H" first="Hanne Ej" last="Meijers-Heijboer">Hanne Ej Meijers-Heijboer</name><affiliation><nlm:aff id="I22">Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wijnen, Juul" sort="Wijnen, Juul" uniqKey="Wijnen J" first="Juul" last="Wijnen">Juul Wijnen</name><affiliation><nlm:aff id="I23">Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="G Mez Garcia, Encarna B" sort="G Mez Garcia, Encarna B" uniqKey="G Mez Garcia E" first="Encarna B" last="G Mez Garcia">Encarna B. G Mez Garcia</name><affiliation><nlm:aff id="I24">Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ligtenberg, Marjolijn J" sort="Ligtenberg, Marjolijn J" uniqKey="Ligtenberg M" first="Marjolijn J" last="Ligtenberg">Marjolijn J. Ligtenberg</name><affiliation><nlm:aff id="I25">Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kriege, Mieke" sort="Kriege, Mieke" uniqKey="Kriege M" first="Mieke" last="Kriege">Mieke Kriege</name><affiliation><nlm:aff id="I26">Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Collee, J Margriet" sort="Collee, J Margriet" uniqKey="Collee J" first="J Margriet" last="Collée">J Margriet Collée</name><affiliation><nlm:aff id="I27">Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ausems, Margreet Gem" sort="Ausems, Margreet Gem" uniqKey="Ausems M" first="Margreet Gem" last="Ausems">Margreet Gem Ausems</name><affiliation><nlm:aff id="I28">Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Oosterwijk, Jan C" sort="Oosterwijk, Jan C" uniqKey="Oosterwijk J" first="Jan C" last="Oosterwijk">Jan C. Oosterwijk</name><affiliation><nlm:aff id="I29">Department of Genetics, University Medical Center, Groningen University, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Peock, Susan" sort="Peock, Susan" uniqKey="Peock S" first="Susan" last="Peock">Susan Peock</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Frost, Debra" sort="Frost, Debra" uniqKey="Frost D" first="Debra" last="Frost">Debra Frost</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Ellis, Steve D" sort="Ellis, Steve D" uniqKey="Ellis S" first="Steve D" last="Ellis">Steve D. Ellis</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Platte, Radka" sort="Platte, Radka" uniqKey="Platte R" first="Radka" last="Platte">Radka Platte</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Fineberg, Elena" sort="Fineberg, Elena" uniqKey="Fineberg E" first="Elena" last="Fineberg">Elena Fineberg</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Evans, D Gareth" sort="Evans, D Gareth" uniqKey="Evans D" first="D Gareth" last="Evans">D Gareth Evans</name><affiliation><nlm:aff id="I31">Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Lalloo, Fiona" sort="Lalloo, Fiona" uniqKey="Lalloo F" first="Fiona" last="Lalloo">Fiona Lalloo</name><affiliation><nlm:aff id="I31">Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Jacobs, Chris" sort="Jacobs, Chris" uniqKey="Jacobs C" first="Chris" last="Jacobs">Chris Jacobs</name><affiliation><nlm:aff id="I32">Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK</nlm:aff></affiliation></author><author><name sortKey="Eeles, Ros" sort="Eeles, Ros" uniqKey="Eeles R" first="Ros" last="Eeles">Ros Eeles</name><affiliation><nlm:aff id="I33">Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, UK</nlm:aff></affiliation></author><author><name sortKey="Adlard, Julian" sort="Adlard, Julian" uniqKey="Adlard J" first="Julian" last="Adlard">Julian Adlard</name><affiliation><nlm:aff id="I34">Yorkshire Regional Genetics Service, Leeds, UK</nlm:aff></affiliation></author><author><name sortKey="Davidson, Rosemarie" sort="Davidson, Rosemarie" uniqKey="Davidson R" first="Rosemarie" last="Davidson">Rosemarie Davidson</name><affiliation><nlm:aff id="I35">Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Cole, Trevor" sort="Cole, Trevor" uniqKey="Cole T" first="Trevor" last="Cole">Trevor Cole</name><affiliation><nlm:aff id="I36">West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK</nlm:aff></affiliation></author><author><name sortKey="Cook, Jackie" sort="Cook, Jackie" uniqKey="Cook J" first="Jackie" last="Cook">Jackie Cook</name><affiliation><nlm:aff id="I37">Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK</nlm:aff></affiliation></author><author><name sortKey="Paterson, Joan" sort="Paterson, Joan" uniqKey="Paterson J" first="Joan" last="Paterson">Joan Paterson</name><affiliation><nlm:aff id="I38">Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Douglas, Fiona" sort="Douglas, Fiona" uniqKey="Douglas F" first="Fiona" last="Douglas">Fiona Douglas</name><affiliation><nlm:aff id="I39">Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK</nlm:aff></affiliation></author><author><name sortKey="Brewer, Carole" sort="Brewer, Carole" uniqKey="Brewer C" first="Carole" last="Brewer">Carole Brewer</name><affiliation><nlm:aff id="I40">Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Hodgson, Shirley" sort="Hodgson, Shirley" uniqKey="Hodgson S" first="Shirley" last="Hodgson">Shirley Hodgson</name><affiliation><nlm:aff id="I41">Medical Genetics Unit, St George's, University of London, UK</nlm:aff></affiliation></author><author><name sortKey="Morrison, Patrick J" sort="Morrison, Patrick J" uniqKey="Morrison P" first="Patrick J" last="Morrison">Patrick J. Morrison</name><affiliation><nlm:aff id="I42">Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, and Department of Medical Genetics, Queens University Belfast, Belfast UK</nlm:aff></affiliation></author><author><name sortKey="Walker, Lisa" sort="Walker, Lisa" uniqKey="Walker L" first="Lisa" last="Walker">Lisa Walker</name><affiliation><nlm:aff id="I43">Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Rogers, Mark T" sort="Rogers, Mark T" uniqKey="Rogers M" first="Mark T" last="Rogers">Mark T. Rogers</name><affiliation><nlm:aff id="I44">All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK</nlm:aff></affiliation></author><author><name sortKey="Donaldson, Alan" sort="Donaldson, Alan" uniqKey="Donaldson A" first="Alan" last="Donaldson">Alan Donaldson</name><affiliation><nlm:aff id="I45">Clinical Genetics Department, St Michael's Hospital, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Dorkins, Huw" sort="Dorkins, Huw" uniqKey="Dorkins H" first="Huw" last="Dorkins">Huw Dorkins</name><affiliation><nlm:aff id="I46">North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, UK</nlm:aff></affiliation></author><author><name sortKey="Godwin, Andrew K" sort="Godwin, Andrew K" uniqKey="Godwin A" first="Andrew K" last="Godwin">Andrew K. Godwin</name><affiliation><nlm:aff id="I47">Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA</nlm:aff></affiliation></author><author><name sortKey="Bove, Betsy" sort="Bove, Betsy" uniqKey="Bove B" first="Betsy" last="Bove">Betsy Bove</name><affiliation><nlm:aff id="I48">Clinical Molecular Genetics Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Stoppa Lyonnet, Dominique" sort="Stoppa Lyonnet, Dominique" uniqKey="Stoppa Lyonnet D" first="Dominique" last="Stoppa-Lyonnet">Dominique Stoppa-Lyonnet</name><affiliation><nlm:aff id="I49">Service de Génétique Oncologique, Institut Curie, Paris, France, Unité INSERM U830, Institut Curie, Paris, France, Université Paris Descartes, Faculté de Médecine, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Houdayer, Claude" sort="Houdayer, Claude" uniqKey="Houdayer C" first="Claude" last="Houdayer">Claude Houdayer</name><affiliation><nlm:aff id="I50">Service de Génétique Oncologique, Institut Curie, Paris, France and Université Paris Descartes, Faculté de Pharmacie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Buecher, Bruno" sort="Buecher, Bruno" uniqKey="Buecher B" first="Bruno" last="Buecher">Bruno Buecher</name><affiliation><nlm:aff id="I51">Service de Génétique Oncologique, Institut Curie, 26 rue d'Ulm, Paris, France</nlm:aff></affiliation></author><author><name sortKey="De Pauw, Antoine" sort="De Pauw, Antoine" uniqKey="De Pauw A" first="Antoine" last="De Pauw">Antoine De Pauw</name><affiliation><nlm:aff id="I52">Service de Génétique Oncologique, Institut Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Mazoyer, Sylvie" sort="Mazoyer, Sylvie" uniqKey="Mazoyer S" first="Sylvie" last="Mazoyer">Sylvie Mazoyer</name><affiliation><nlm:aff id="I53">INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Calender, Alain" sort="Calender, Alain" uniqKey="Calender A" first="Alain" last="Calender">Alain Calender</name><affiliation><nlm:aff id="I54">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon Bérard, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Leone, Melanie" sort="Leone, Melanie" uniqKey="Leone M" first="Mélanie" last="Léoné">Mélanie Léoné</name><affiliation><nlm:aff id="I54">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon Bérard, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Bressac De Paillerets, Brigitte" sort="Bressac De Paillerets, Brigitte" uniqKey="Bressac De Paillerets B" first="Brigitte" last="Bressac- De Paillerets">Brigitte Bressac- De Paillerets</name><affiliation><nlm:aff id="I55">Service de Génétique, Institut de Cancérologie Gustave Roussy, Villejuif, France and INSERM U946, Fondation Jean Dausset, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Caron, Olivier" sort="Caron, Olivier" uniqKey="Caron O" first="Olivier" last="Caron">Olivier Caron</name><affiliation><nlm:aff id="I56">Consultation de Génétique, Département de Médecine, Institut de Cancérologie Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="Sobol, Hagay" sort="Sobol, Hagay" uniqKey="Sobol H" first="Hagay" last="Sobol">Hagay Sobol</name><affiliation><nlm:aff id="I57">Département Oncologie génétique, Prévention et Dépistage, INSERM CIC-P9502, Institut Paoli-Calmettes/Université d'Aix-Marseille II, Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Frenay, Marc" sort="Frenay, Marc" uniqKey="Frenay M" first="Marc" last="Frenay">Marc Frenay</name><affiliation><nlm:aff id="I58">Centre Antoine Lacassagne, Nice, France</nlm:aff></affiliation></author><author><name sortKey="Prieur, Fabienne" sort="Prieur, Fabienne" uniqKey="Prieur F" first="Fabienne" last="Prieur">Fabienne Prieur</name><affiliation><nlm:aff id="I59">Service de Génétique Clinique Chromosomique et Moléculaire, Centre Hospitalier Universitaire de St Etienne, St Etienne, France</nlm:aff></affiliation></author><author><name sortKey="Ferrer, Sandra Fert" sort="Ferrer, Sandra Fert" uniqKey="Ferrer S" first="Sandra Fert" last="Ferrer">Sandra Fert Ferrer</name><affiliation><nlm:aff id="I60">Laboratoire de Génétique Chromosomique, Hôtel Dieu Centre Hospitalier, BP 1125 Chambéry, France</nlm:aff></affiliation></author><author><name sortKey="Mortemousque, Isabelle" sort="Mortemousque, Isabelle" uniqKey="Mortemousque I" first="Isabelle" last="Mortemousque">Isabelle Mortemousque</name><affiliation><nlm:aff id="I61">Service de Génétique, Centre Hospitalier Universitaire Bretonneau, Tours, France</nlm:aff></affiliation></author><author><name sortKey="Buys, Saundra" sort="Buys, Saundra" uniqKey="Buys S" first="Saundra" last="Buys">Saundra Buys</name><affiliation><nlm:aff id="I63">Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA</nlm:aff></affiliation></author><author><name sortKey="Daly, Mary" sort="Daly, Mary" uniqKey="Daly M" first="Mary" last="Daly">Mary Daly</name><affiliation><nlm:aff id="I64">Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA</nlm:aff></affiliation></author><author><name sortKey="Miron, Alexander" sort="Miron, Alexander" uniqKey="Miron A" first="Alexander" last="Miron">Alexander Miron</name><affiliation><nlm:aff id="I65">Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Surgery, Harvard Medical School, 27 Drydock Avenue, Boston, MA 02210, USA</nlm:aff></affiliation></author><author><name sortKey="Terry, Mary Beth" sort="Terry, Mary Beth" uniqKey="Terry M" first="Mary Beth" last="Terry">Mary Beth Terry</name><affiliation><nlm:aff id="I66">Department of Epidemiology, Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L" last="Hopper">John L. Hopper</name><affiliation><nlm:aff id="I67">Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Melbourne School of Population Health, Level 1, 723 Swanston Street, The University of Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="John, Esther M" sort="John, Esther M" uniqKey="John E" first="Esther M" last="John">Esther M. John</name><affiliation><nlm:aff id="I68">Department of Epidemiology, Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538, USA</nlm:aff></affiliation></author><author><name sortKey="Southey, Melissa" sort="Southey, Melissa" uniqKey="Southey M" first="Melissa" last="Southey">Melissa Southey</name><affiliation><nlm:aff id="I69">Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Goldgar, David" sort="Goldgar, David" uniqKey="Goldgar D" first="David" last="Goldgar">David Goldgar</name><affiliation><nlm:aff id="I70">Department of Dermatology, University of Utah School of Medicine, 30 North 1900 East, SOM 4B454, Salt Lake City, UT 84132, USA</nlm:aff></affiliation></author><author><name sortKey="Singer, Christian F" sort="Singer, Christian F" uniqKey="Singer C" first="Christian F" last="Singer">Christian F. Singer</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Fink Retter, Anneliese" sort="Fink Retter, Anneliese" uniqKey="Fink Retter A" first="Anneliese" last="Fink-Retter">Anneliese Fink-Retter</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Tea, Muy Kheng" sort="Tea, Muy Kheng" uniqKey="Tea M" first="Muy-Kheng" last="Tea">Muy-Kheng Tea</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Kaulich, Daphne Geschwantler" sort="Kaulich, Daphne Geschwantler" uniqKey="Kaulich D" first="Daphne Geschwantler" last="Kaulich">Daphne Geschwantler Kaulich</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Hansen, Thomas Vo" sort="Hansen, Thomas Vo" uniqKey="Hansen T" first="Thomas Vo" last="Hansen">Thomas Vo Hansen</name><affiliation><nlm:aff id="I72">Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Nielsen, Finn C" sort="Nielsen, Finn C" uniqKey="Nielsen F" first="Finn C" last="Nielsen">Finn C. Nielsen</name><affiliation><nlm:aff id="I72">Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Barkardottir, Rosa B" sort="Barkardottir, Rosa B" uniqKey="Barkardottir R" first="Rosa B" last="Barkardottir">Rosa B. Barkardottir</name><affiliation><nlm:aff id="I73">Department of Pathology, Landspitali - University Hospital, Reykjavik Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Gaudet, Mia" sort="Gaudet, Mia" uniqKey="Gaudet M" first="Mia" last="Gaudet">Mia Gaudet</name><affiliation><nlm:aff id="I74">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Kirchhoff, Tomas" sort="Kirchhoff, Tomas" uniqKey="Kirchhoff T" first="Tomas" last="Kirchhoff">Tomas Kirchhoff</name><affiliation><nlm:aff id="I75">Department of Environmental Medicine, NYU Cancer Institute, New York University School of Medicine, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Joseph, Vijai" sort="Joseph, Vijai" uniqKey="Joseph V" first="Vijai" last="Joseph">Vijai Joseph</name><affiliation><nlm:aff id="I76">Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Dutra Clarke, Ana" sort="Dutra Clarke, Ana" uniqKey="Dutra Clarke A" first="Ana" last="Dutra-Clarke">Ana Dutra-Clarke</name><affiliation><nlm:aff id="I76">Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Offit, Kenneth" sort="Offit, Kenneth" uniqKey="Offit K" first="Kenneth" last="Offit">Kenneth Offit</name><affiliation><nlm:aff id="I76">Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Piedmonte, Marion" sort="Piedmonte, Marion" uniqKey="Piedmonte M" first="Marion" last="Piedmonte">Marion Piedmonte</name><affiliation><nlm:aff id="I77">Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Kirk, Judy" sort="Kirk, Judy" uniqKey="Kirk J" first="Judy" last="Kirk">Judy Kirk</name><affiliation><nlm:aff id="I78">Australia New Zealand (ANZGOG), Westmead Hospital, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Cohn, David" sort="Cohn, David" uniqKey="Cohn D" first="David" last="Cohn">David Cohn</name><affiliation><nlm:aff id="I79">Ohio State University, Columbus Cancer Council, Columbus, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Hurteau, Jean" sort="Hurteau, Jean" uniqKey="Hurteau J" first="Jean" last="Hurteau">Jean Hurteau</name><affiliation><nlm:aff id="I80">Evanston CCOP - NorthShore University Health System; University of Chicago, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Byron, John" sort="Byron, John" uniqKey="Byron J" first="John" last="Byron">John Byron</name><affiliation><nlm:aff id="I81">Southern Pines Women's Health Center, P.C., University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Fiorica, James" sort="Fiorica, James" uniqKey="Fiorica J" first="James" last="Fiorica">James Fiorica</name><affiliation><nlm:aff id="I82">Sarasota Memorial Healthcare, Tufts Medical Center, Sarasota, Florida, USA</nlm:aff></affiliation></author><author><name sortKey="Toland, Amanda E" sort="Toland, Amanda E" uniqKey="Toland A" first="Amanda E" last="Toland">Amanda E. Toland</name><affiliation><nlm:aff id="I83">Department of Molecular Virology, Immunology and Medical Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA</nlm:aff></affiliation></author><author><name sortKey="Montagna, Marco" sort="Montagna, Marco" uniqKey="Montagna M" first="Marco" last="Montagna">Marco Montagna</name><affiliation><nlm:aff id="I84">Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy</nlm:aff></affiliation></author><author><name sortKey="Oliani, Cristina" sort="Oliani, Cristina" uniqKey="Oliani C" first="Cristina" last="Oliani">Cristina Oliani</name><affiliation><nlm:aff id="I85">U.O.C. di Oncologia, ULSS5 Ovest Vicentino, Italy</nlm:aff></affiliation></author><author><name sortKey="Imyanitov, Evgeny" sort="Imyanitov, Evgeny" uniqKey="Imyanitov E" first="Evgeny" last="Imyanitov">Evgeny Imyanitov</name><affiliation><nlm:aff id="I86">Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, St.-Petersburg, Russia</nlm:aff></affiliation></author><author><name sortKey="Isaacs, Claudine" sort="Isaacs, Claudine" uniqKey="Isaacs C" first="Claudine" last="Isaacs">Claudine Isaacs</name><affiliation><nlm:aff id="I87">Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA</nlm:aff></affiliation></author><author><name sortKey="Tihomirova, Laima" sort="Tihomirova, Laima" uniqKey="Tihomirova L" first="Laima" last="Tihomirova">Laima Tihomirova</name><affiliation><nlm:aff id="I88">Latvian Biomedical Research and Study Centre, Latvia</nlm:aff></affiliation></author><author><name sortKey="Blanco, Ignacio" sort="Blanco, Ignacio" uniqKey="Blanco I" first="Ignacio" last="Blanco">Ignacio Blanco</name><affiliation><nlm:aff id="I89">Genetic Counselling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Lazaro, Conxi" sort="Lazaro, Conxi" uniqKey="Lazaro C" first="Conxi" last="Lazaro">Conxi Lazaro</name><affiliation><nlm:aff id="I90">Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Teule, Alex" sort="Teule, Alex" uniqKey="Teule A" first="Alex" last="Teulé">Alex Teulé</name><affiliation><nlm:aff id="I89">Genetic Counselling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Valle, J Del" sort="Valle, J Del" uniqKey="Valle J" first="J Del" last="Valle">J Del Valle</name><affiliation><nlm:aff id="I90">Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A" last="Gayther">Simon A. Gayther</name><affiliation><nlm:aff id="I91">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Odunsi, Kunle" sort="Odunsi, Kunle" uniqKey="Odunsi K" first="Kunle" last="Odunsi">Kunle Odunsi</name><affiliation><nlm:aff id="I92">Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Gross, Jenny" sort="Gross, Jenny" uniqKey="Gross J" first="Jenny" last="Gross">Jenny Gross</name><affiliation><nlm:aff id="I93">Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Karlan, Beth Y" sort="Karlan, Beth Y" uniqKey="Karlan B" first="Beth Y" last="Karlan">Beth Y. Karlan</name><affiliation><nlm:aff id="I93">Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Olah, Edith" sort="Olah, Edith" uniqKey="Olah E" first="Edith" last="Olah">Edith Olah</name><affiliation><nlm:aff id="I94">Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary</nlm:aff></affiliation></author><author><name sortKey="Teo, Soo Hwang" sort="Teo, Soo Hwang" uniqKey="Teo S" first="Soo-Hwang" last="Teo">Soo-Hwang Teo</name><affiliation><nlm:aff id="I95">Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Malaysia and University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Ganz, Patricia A" sort="Ganz, Patricia A" uniqKey="Ganz P" first="Patricia A" last="Ganz">Patricia A. Ganz</name><affiliation><nlm:aff id="I96">Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Beattie, Mary S" sort="Beattie, Mary S" uniqKey="Beattie M" first="Mary S" last="Beattie">Mary S. Beattie</name><affiliation><nlm:aff id="I97">UCSF Cancer Risk Program, University of California, San Francisco, CA; UCSF Departments of Medicine, Epidemiology, and Biostatistics, Sand Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Dorfling, Cecelia M" sort="Dorfling, Cecelia M" uniqKey="Dorfling C" first="Cecelia M" last="Dorfling">Cecelia M. Dorfling</name><affiliation><nlm:aff id="I98">Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, South Africa</nlm:aff></affiliation></author><author><name sortKey="Van Rensburg, Elizabeth Jansen" sort="Van Rensburg, Elizabeth Jansen" uniqKey="Van Rensburg E" first="Elizabeth Jansen" last="Van Rensburg">Elizabeth Jansen Van Rensburg</name><affiliation><nlm:aff id="I98">Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, South Africa</nlm:aff></affiliation></author><author><name sortKey="Diez, Orland" sort="Diez, Orland" uniqKey="Diez O" first="Orland" last="Diez">Orland Diez</name><affiliation><nlm:aff id="I99">Oncogenetics Laboratory. Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital. Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Kwong, Ava" sort="Kwong, Ava" uniqKey="Kwong A" first="Ava" last="Kwong">Ava Kwong</name><affiliation><nlm:aff id="I100">The Hong Kong Hereditary Breast Cancer Family Registry; The Universtiy of Hong Kong; Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong</nlm:aff></affiliation></author><author><name sortKey="Schmutzler, Rita K" sort="Schmutzler, Rita K" uniqKey="Schmutzler R" first="Rita K" last="Schmutzler">Rita K. Schmutzler</name><affiliation><nlm:aff id="I101">Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), University hospital of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Wappenschmidt, Barbara" sort="Wappenschmidt, Barbara" uniqKey="Wappenschmidt B" first="Barbara" last="Wappenschmidt">Barbara Wappenschmidt</name><affiliation><nlm:aff id="I101">Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), University hospital of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Engel, Christoph" sort="Engel, Christoph" uniqKey="Engel C" first="Christoph" last="Engel">Christoph Engel</name><affiliation><nlm:aff id="I102">Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany</nlm:aff></affiliation></author><author><name sortKey="Meindl, Alfons" sort="Meindl, Alfons" uniqKey="Meindl A" first="Alfons" last="Meindl">Alfons Meindl</name><affiliation><nlm:aff id="I103">Department of Gynaecology and Obstetrics, Division of Tumour Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Ditsch, Nina" sort="Ditsch, Nina" uniqKey="Ditsch N" first="Nina" last="Ditsch">Nina Ditsch</name><affiliation><nlm:aff id="I104">Department of Gynaecology and Obstetrics, Ludwig-Maximilian University Munich, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Arnold, Norbert" sort="Arnold, Norbert" uniqKey="Arnold N" first="Norbert" last="Arnold">Norbert Arnold</name><affiliation><nlm:aff id="I105">Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Heidemann, Simone" sort="Heidemann, Simone" uniqKey="Heidemann S" first="Simone" last="Heidemann">Simone Heidemann</name><affiliation><nlm:aff id="I106">Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Niederacher, Dieter" sort="Niederacher, Dieter" uniqKey="Niederacher D" first="Dieter" last="Niederacher">Dieter Niederacher</name><affiliation><nlm:aff id="I107">Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany</nlm:aff></affiliation></author><author><name sortKey="Preisler Adams, Sabine" sort="Preisler Adams, Sabine" uniqKey="Preisler Adams S" first="Sabine" last="Preisler-Adams">Sabine Preisler-Adams</name><affiliation><nlm:aff id="I108">Institute of Human Genetics, University of Münster, Münster, Germany</nlm:aff></affiliation></author><author><name sortKey="Gadzicki, Dorothea" sort="Gadzicki, Dorothea" uniqKey="Gadzicki D" first="Dorothea" last="Gadzicki">Dorothea Gadzicki</name><affiliation><nlm:aff id="I109">Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany</nlm:aff></affiliation></author><author><name sortKey="Varon Mateeva, Raymonda" sort="Varon Mateeva, Raymonda" uniqKey="Varon Mateeva R" first="Raymonda" last="Varon-Mateeva">Raymonda Varon-Mateeva</name><affiliation><nlm:aff id="I110">Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin, Germany</nlm:aff></affiliation></author><author><name sortKey="Deissler, Helmut" sort="Deissler, Helmut" uniqKey="Deissler H" first="Helmut" last="Deissler">Helmut Deissler</name><affiliation><nlm:aff id="I111">Department of Gynaecology and Obstetrics, University Hospital Ulm, Germany</nlm:aff></affiliation></author><author><name sortKey="Gehrig, Andrea" sort="Gehrig, Andrea" uniqKey="Gehrig A" first="Andrea" last="Gehrig">Andrea Gehrig</name><affiliation><nlm:aff id="I112">Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Sutter, Christian" sort="Sutter, Christian" uniqKey="Sutter C" first="Christian" last="Sutter">Christian Sutter</name><affiliation><nlm:aff id="I113">Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Kast, Karin" sort="Kast, Karin" uniqKey="Kast K" first="Karin" last="Kast">Karin Kast</name><affiliation><nlm:aff id="I114">Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University. Dresden, Germany</nlm:aff></affiliation></author><author><name sortKey="Fiebig, Britta" sort="Fiebig, Britta" uniqKey="Fiebig B" first="Britta" last="Fiebig">Britta Fiebig</name><affiliation><nlm:aff id="I115">Institute of Human Genetics, University Regensburg, Regensbirg. Germany</nlm:aff></affiliation></author><author><name sortKey="Sch Fer, Dieter" sort="Sch Fer, Dieter" uniqKey="Sch Fer D" first="Dieter" last="Sch Fer">Dieter Sch Fer</name><affiliation><nlm:aff id="I116">Institute of Human Genetics, University Hospital Frankfurt a.M., Germany Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Caldes, Trinidad" sort="Caldes, Trinidad" uniqKey="Caldes T" first="Trinidad" last="Caldes">Trinidad Caldes</name><affiliation><nlm:aff id="I117">Molecular Oncology Laboratory, Hospital Clinico San Carlos, Martin Lagos s/n, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="De La Hoya, Miguel" sort="De La Hoya, Miguel" uniqKey="De La Hoya M" first="Miguel" last="De La Hoya">Miguel De La Hoya</name><affiliation><nlm:aff id="I117">Molecular Oncology Laboratory, Hospital Clinico San Carlos, Martin Lagos s/n, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name><affiliation><nlm:aff id="I118">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. BOX 700, 00029 HUS, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Muranen, Taru A" sort="Muranen, Taru A" uniqKey="Muranen T" first="Taru A" last="Muranen">Taru A. Muranen</name><affiliation><nlm:aff id="I118">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. BOX 700, 00029 HUS, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Lesperance, Bernard" sort="Lesperance, Bernard" uniqKey="Lesperance B" first="Bernard" last="Lespérance">Bernard Lespérance</name><affiliation><nlm:aff id="I119">Faculty of Medicine - Medicine and Medical Specialties, Université de Montréal Hemato-oncology service, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin Blvd West Montreal, QC, Canada</nlm:aff></affiliation></author><author><name sortKey="Spurdle, Amanda B" sort="Spurdle, Amanda B" uniqKey="Spurdle A" first="Amanda B" last="Spurdle">Amanda B. Spurdle</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Neuhausen, Susan L" sort="Neuhausen, Susan L" uniqKey="Neuhausen S" first="Susan L" last="Neuhausen">Susan L. Neuhausen</name><affiliation><nlm:aff id="I121">Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ding, Yuan C" sort="Ding, Yuan C" uniqKey="Ding Y" first="Yuan C" last="Ding">Yuan C. Ding</name><affiliation><nlm:aff id="I121">Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Xianshu" sort="Wang, Xianshu" uniqKey="Wang X" first="Xianshu" last="Wang">Xianshu Wang</name><affiliation><nlm:aff id="I122">Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Fredericksen, Zachary" sort="Fredericksen, Zachary" uniqKey="Fredericksen Z" first="Zachary" last="Fredericksen">Zachary Fredericksen</name><affiliation><nlm:aff id="I123">Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Pankratz, Vernon S" sort="Pankratz, Vernon S" uniqKey="Pankratz V" first="Vernon S" last="Pankratz">Vernon S. Pankratz</name><affiliation><nlm:aff id="I123">Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Lindor, Noralane M" sort="Lindor, Noralane M" uniqKey="Lindor N" first="Noralane M" last="Lindor">Noralane M. Lindor</name><affiliation><nlm:aff id="I124">Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Peterlongo, Paolo" sort="Peterlongo, Paolo" uniqKey="Peterlongo P" first="Paolo" last="Peterlongo">Paolo Peterlongo</name><affiliation><nlm:aff id="I125">Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Manoukian, Siranoush" sort="Manoukian, Siranoush" uniqKey="Manoukian S" first="Siranoush" last="Manoukian">Siranoush Manoukian</name><affiliation><nlm:aff id="I126">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Peissel, Bernard" sort="Peissel, Bernard" uniqKey="Peissel B" first="Bernard" last="Peissel">Bernard Peissel</name><affiliation><nlm:aff id="I126">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Zaffaroni, Daniela" sort="Zaffaroni, Daniela" uniqKey="Zaffaroni D" first="Daniela" last="Zaffaroni">Daniela Zaffaroni</name><affiliation><nlm:aff id="I126">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Bonanni, Bernardo" sort="Bonanni, Bernardo" uniqKey="Bonanni B" first="Bernardo" last="Bonanni">Bernardo Bonanni</name><affiliation><nlm:aff id="I127">Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan Italy</nlm:aff></affiliation></author><author><name sortKey="Bernard, Loris" sort="Bernard, Loris" uniqKey="Bernard L" first="Loris" last="Bernard">Loris Bernard</name><affiliation><nlm:aff id="I128">Department of Experimental Oncology, Istituto Europeo di Oncologia, Milan, Italy and Consortium for Genomics Technology (Cogentech), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Dolcetti, Riccardo" sort="Dolcetti, Riccardo" uniqKey="Dolcetti R" first="Riccardo" last="Dolcetti">Riccardo Dolcetti</name><affiliation><nlm:aff id="I129">Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy</nlm:aff></affiliation></author><author><name sortKey="Papi, Laura" sort="Papi, Laura" uniqKey="Papi L" first="Laura" last="Papi">Laura Papi</name><affiliation><nlm:aff id="I130">Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Firenze, Italy</nlm:aff></affiliation></author><author><name sortKey="Ottini, Laura" sort="Ottini, Laura" uniqKey="Ottini L" first="Laura" last="Ottini">Laura Ottini</name><affiliation><nlm:aff id="I131">Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Radice, Paolo" sort="Radice, Paolo" uniqKey="Radice P" first="Paolo" last="Radice">Paolo Radice</name><affiliation><nlm:aff id="I125">Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Greene, Mark H" sort="Greene, Mark H" uniqKey="Greene M" first="Mark H" last="Greene">Mark H. Greene</name><affiliation><nlm:aff id="I132">Clinical Genetics Branch, DCEG, NCI; Room EPS 7032, Rockville, MD 20852, USA</nlm:aff></affiliation></author><author><name sortKey="Loud, Jennifer T" sort="Loud, Jennifer T" uniqKey="Loud J" first="Jennifer T" last="Loud">Jennifer T. Loud</name><affiliation><nlm:aff id="I132">Clinical Genetics Branch, DCEG, NCI; Room EPS 7032, Rockville, MD 20852, USA</nlm:aff></affiliation></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L" last="Andrulis">Irene L. Andrulis</name><affiliation><nlm:aff id="I133">Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON; Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Ozcelik, Hilmi" sort="Ozcelik, Hilmi" uniqKey="Ozcelik H" first="Hilmi" last="Ozcelik">Hilmi Ozcelik</name><affiliation><nlm:aff id="I134">Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Mulligan, Anna Marie" sort="Mulligan, Anna Marie" uniqKey="Mulligan A" first="Anna Marie" last="Mulligan">Anna Marie Mulligan</name><affiliation><nlm:aff id="I135">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine, and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name><affiliation><nlm:aff id="I136">Ontario Cancer Genetics Network: Cancer Care Ontario, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Thomassen, Mads" sort="Thomassen, Mads" uniqKey="Thomassen M" first="Mads" last="Thomassen">Mads Thomassen</name><affiliation><nlm:aff id="I137">Department of Clinical Genetics, Odense University Hospital, Denmark</nlm:aff></affiliation></author><author><name sortKey="Gerdes, Anne Marie" sort="Gerdes, Anne Marie" uniqKey="Gerdes A" first="Anne-Marie" last="Gerdes">Anne-Marie Gerdes</name><affiliation><nlm:aff id="I138">Department of Clincial Genetics, Rigshospital and Copenhagen University, Denmark</nlm:aff></affiliation></author><author><name sortKey="Jensen, Uffe B" sort="Jensen, Uffe B" uniqKey="Jensen U" first="Uffe B" last="Jensen">Uffe B. Jensen</name><affiliation><nlm:aff id="I139">Department of Clinical Genetics, Skejby Hospital, Aarhus, Denmark</nlm:aff></affiliation></author><author><name sortKey="Skytte, Anne Bine" sort="Skytte, Anne Bine" uniqKey="Skytte A" first="Anne-Bine" last="Skytte">Anne-Bine Skytte</name><affiliation><nlm:aff id="I140">Department of Clinical Genetics, Vejle Hospital, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kruse, Torben A" sort="Kruse, Torben A" uniqKey="Kruse T" first="Torben A" last="Kruse">Torben A. Kruse</name><affiliation><nlm:aff id="I137">Department of Clinical Genetics, Odense University Hospital, Denmark</nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J" last="Couch">Fergus J. Couch</name><affiliation><nlm:aff id="I141">Department of Laboratory Medicine and Pathology, and Health Sciences Research, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Simard, Jacques" sort="Simard, Jacques" uniqKey="Simard J" first="Jacques" last="Simard">Jacques Simard</name><affiliation><nlm:aff id="I142">Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, T3-57, Quebec City and Canada Research Chair in Oncogenetics, Department of Molecular Medicine, Faculty of Medicine, Laval University, QC, Canada</nlm:aff></affiliation></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F" last="Easton">Douglas F. Easton</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22348646</idno><idno type="pmc">3496151</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496151</idno><idno type="RBID">PMC:3496151</idno><idno type="doi">10.1186/bcr3121</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">001623</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001623</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Common variants at 12p11, 12q24, 9p21, 9q31.2 and in <italic>ZNF365 </italic>are associated with breast cancer risk for <italic>BRCA1 </italic>and/or <italic>BRCA2 </italic>mutation carriers</title><author><name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C" last="Antoniou">Antonis C. Antoniou</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Kuchenbaecker, Karoline B" sort="Kuchenbaecker, Karoline B" uniqKey="Kuchenbaecker K" first="Karoline B" last="Kuchenbaecker">Karoline B. Kuchenbaecker</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Soucy, Penny" sort="Soucy, Penny" uniqKey="Soucy P" first="Penny" last="Soucy">Penny Soucy</name><affiliation><nlm:aff id="I2">Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, T3-57, Quebec City, QC Canada</nlm:aff></affiliation></author><author><name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Chen, Xiaoqing" sort="Chen, Xiaoqing" uniqKey="Chen X" first="Xiaoqing" last="Chen">Xiaoqing Chen</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcguffog, Lesley" sort="Mcguffog, Lesley" uniqKey="Mcguffog L" first="Lesley" last="Mcguffog">Lesley Mcguffog</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Lee, Andrew" sort="Lee, Andrew" uniqKey="Lee A" first="Andrew" last="Lee">Andrew Lee</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Barrowdale, Daniel" sort="Barrowdale, Daniel" uniqKey="Barrowdale D" first="Daniel" last="Barrowdale">Daniel Barrowdale</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Sinilnikova, Olga M" sort="Sinilnikova, Olga M" uniqKey="Sinilnikova O" first="Olga M" last="Sinilnikova">Olga M. Sinilnikova</name><affiliation><nlm:aff id="I4">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, 28 rue Laënnec, Lyon 69373, France and INSERM U1052, CNRS UMR5286, Université Lyon 1, Cancer Research Center of Lyon, 28 rue Laënnec, Lyon 69373, France</nlm:aff></affiliation></author><author><name sortKey="Caligo, Maria A" sort="Caligo, Maria A" uniqKey="Caligo M" first="Maria A" last="Caligo">Maria A. Caligo</name><affiliation><nlm:aff id="I5">Section of Genetic Oncology, Dept. of Laboratory Medicine, University and University Hospital of Pisa, Via Roma 57, 56125 Pisa, Italy</nlm:aff></affiliation></author><author><name sortKey="Loman, Niklas" sort="Loman, Niklas" uniqKey="Loman N" first="Niklas" last="Loman">Niklas Loman</name><affiliation><nlm:aff id="I6">Department of Oncology, Lund University Hospital, Lund, Sweden</nlm:aff></affiliation></author><author><name sortKey="Harbst, Katja" sort="Harbst, Katja" uniqKey="Harbst K" first="Katja" last="Harbst">Katja Harbst</name><affiliation><nlm:aff id="I6">Department of Oncology, Lund University Hospital, Lund, Sweden</nlm:aff></affiliation></author><author><name sortKey="Lindblom, Annika" sort="Lindblom, Annika" uniqKey="Lindblom A" first="Annika" last="Lindblom">Annika Lindblom</name><affiliation><nlm:aff id="I7">Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Arver, Brita" sort="Arver, Brita" uniqKey="Arver B" first="Brita" last="Arver">Brita Arver</name><affiliation><nlm:aff id="I8">Department of Oncology, Karolinska University Hospital, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rosenquist, Richard" sort="Rosenquist, Richard" uniqKey="Rosenquist R" first="Richard" last="Rosenquist">Richard Rosenquist</name><affiliation><nlm:aff id="I9">Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Karlsson, Per" sort="Karlsson, Per" uniqKey="Karlsson P" first="Per" last="Karlsson">Per Karlsson</name><affiliation><nlm:aff id="I10">Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Nathanson, Kate" sort="Nathanson, Kate" uniqKey="Nathanson K" first="Kate" last="Nathanson">Kate Nathanson</name><affiliation><nlm:aff id="I11">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Domchek, Susan" sort="Domchek, Susan" uniqKey="Domchek S" first="Susan" last="Domchek">Susan Domchek</name><affiliation><nlm:aff id="I11">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Rebbeck, Tim" sort="Rebbeck, Tim" uniqKey="Rebbeck T" first="Tim" last="Rebbeck">Tim Rebbeck</name><affiliation><nlm:aff id="I11">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Jakubowska, Anna" sort="Jakubowska, Anna" uniqKey="Jakubowska A" first="Anna" last="Jakubowska">Anna Jakubowska</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Lubinski, Jan" sort="Lubinski, Jan" uniqKey="Lubinski J" first="Jan" last="Lubinski">Jan Lubinski</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Jaworska, Katarzyna" sort="Jaworska, Katarzyna" uniqKey="Jaworska K" first="Katarzyna" last="Jaworska">Katarzyna Jaworska</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Durda, Katarzyna" sort="Durda, Katarzyna" uniqKey="Durda K" first="Katarzyna" last="Durda">Katarzyna Durda</name><affiliation><nlm:aff id="I13">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin and Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland</nlm:aff></affiliation></author><author><name sortKey="Zlowowcka Perlowska, El Bieta" sort="Zlowowcka Perlowska, El Bieta" uniqKey="Zlowowcka Perlowska E" first="El Bieta" last="Złowowcka-Perłowska">El Bieta Złowowcka-Perłowska</name><affiliation><nlm:aff id="I12">Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</nlm:aff></affiliation></author><author><name sortKey="Osorio, Ana" sort="Osorio, Ana" uniqKey="Osorio A" first="Ana" last="Osorio">Ana Osorio</name><affiliation><nlm:aff id="I14">Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain and Spanish Network on Rare Diseases (CIBERER)</nlm:aff></affiliation></author><author><name sortKey="Duran, Mercedes" sort="Duran, Mercedes" uniqKey="Duran M" first="Mercedes" last="Durán">Mercedes Durán</name><affiliation><nlm:aff id="I15">Institute of Biology and Molecular Genetics. Universidad de Valladolid (IBGM-UVA), Valladolid, Spain</nlm:aff></affiliation></author><author><name sortKey="Andres, Raquel" sort="Andres, Raquel" uniqKey="Andres R" first="Raquel" last="Andrés">Raquel Andrés</name><affiliation><nlm:aff id="I16">Oncology unit. Hospital clinico Universitario "Lozano Blesa", Zaragoza, Spain</nlm:aff></affiliation></author><author><name sortKey="Benitez, Javier" sort="Benitez, Javier" uniqKey="Benitez J" first="Javier" last="Benítez">Javier Benítez</name><affiliation><nlm:aff id="I17">Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain and Spanish Network on Rare Diseases (CIBERER)</nlm:aff></affiliation></author><author><name sortKey="Hamann, Ute" sort="Hamann, Ute" uniqKey="Hamann U" first="Ute" last="Hamann">Ute Hamann</name><affiliation><nlm:aff id="I18">Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Hogervorst, Frans B" sort="Hogervorst, Frans B" uniqKey="Hogervorst F" first="Frans B" last="Hogervorst">Frans B. Hogervorst</name><affiliation><nlm:aff id="I19">Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Os, Theo A" sort="Van Os, Theo A" uniqKey="Van Os T" first="Theo A" last="Van Os">Theo A. Van Os</name><affiliation><nlm:aff id="I20">Department of Clinical Genetics, Academic Meical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Verhoef, Senno" sort="Verhoef, Senno" uniqKey="Verhoef S" first="Senno" last="Verhoef">Senno Verhoef</name><affiliation><nlm:aff id="I21">Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Meijers Heijboer, Hanne Ej" sort="Meijers Heijboer, Hanne Ej" uniqKey="Meijers Heijboer H" first="Hanne Ej" last="Meijers-Heijboer">Hanne Ej Meijers-Heijboer</name><affiliation><nlm:aff id="I22">Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wijnen, Juul" sort="Wijnen, Juul" uniqKey="Wijnen J" first="Juul" last="Wijnen">Juul Wijnen</name><affiliation><nlm:aff id="I23">Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="G Mez Garcia, Encarna B" sort="G Mez Garcia, Encarna B" uniqKey="G Mez Garcia E" first="Encarna B" last="G Mez Garcia">Encarna B. G Mez Garcia</name><affiliation><nlm:aff id="I24">Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ligtenberg, Marjolijn J" sort="Ligtenberg, Marjolijn J" uniqKey="Ligtenberg M" first="Marjolijn J" last="Ligtenberg">Marjolijn J. Ligtenberg</name><affiliation><nlm:aff id="I25">Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kriege, Mieke" sort="Kriege, Mieke" uniqKey="Kriege M" first="Mieke" last="Kriege">Mieke Kriege</name><affiliation><nlm:aff id="I26">Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Collee, J Margriet" sort="Collee, J Margriet" uniqKey="Collee J" first="J Margriet" last="Collée">J Margriet Collée</name><affiliation><nlm:aff id="I27">Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ausems, Margreet Gem" sort="Ausems, Margreet Gem" uniqKey="Ausems M" first="Margreet Gem" last="Ausems">Margreet Gem Ausems</name><affiliation><nlm:aff id="I28">Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Oosterwijk, Jan C" sort="Oosterwijk, Jan C" uniqKey="Oosterwijk J" first="Jan C" last="Oosterwijk">Jan C. Oosterwijk</name><affiliation><nlm:aff id="I29">Department of Genetics, University Medical Center, Groningen University, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Peock, Susan" sort="Peock, Susan" uniqKey="Peock S" first="Susan" last="Peock">Susan Peock</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Frost, Debra" sort="Frost, Debra" uniqKey="Frost D" first="Debra" last="Frost">Debra Frost</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Ellis, Steve D" sort="Ellis, Steve D" uniqKey="Ellis S" first="Steve D" last="Ellis">Steve D. Ellis</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Platte, Radka" sort="Platte, Radka" uniqKey="Platte R" first="Radka" last="Platte">Radka Platte</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Fineberg, Elena" sort="Fineberg, Elena" uniqKey="Fineberg E" first="Elena" last="Fineberg">Elena Fineberg</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Evans, D Gareth" sort="Evans, D Gareth" uniqKey="Evans D" first="D Gareth" last="Evans">D Gareth Evans</name><affiliation><nlm:aff id="I31">Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Lalloo, Fiona" sort="Lalloo, Fiona" uniqKey="Lalloo F" first="Fiona" last="Lalloo">Fiona Lalloo</name><affiliation><nlm:aff id="I31">Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Jacobs, Chris" sort="Jacobs, Chris" uniqKey="Jacobs C" first="Chris" last="Jacobs">Chris Jacobs</name><affiliation><nlm:aff id="I32">Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK</nlm:aff></affiliation></author><author><name sortKey="Eeles, Ros" sort="Eeles, Ros" uniqKey="Eeles R" first="Ros" last="Eeles">Ros Eeles</name><affiliation><nlm:aff id="I33">Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, UK</nlm:aff></affiliation></author><author><name sortKey="Adlard, Julian" sort="Adlard, Julian" uniqKey="Adlard J" first="Julian" last="Adlard">Julian Adlard</name><affiliation><nlm:aff id="I34">Yorkshire Regional Genetics Service, Leeds, UK</nlm:aff></affiliation></author><author><name sortKey="Davidson, Rosemarie" sort="Davidson, Rosemarie" uniqKey="Davidson R" first="Rosemarie" last="Davidson">Rosemarie Davidson</name><affiliation><nlm:aff id="I35">Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Cole, Trevor" sort="Cole, Trevor" uniqKey="Cole T" first="Trevor" last="Cole">Trevor Cole</name><affiliation><nlm:aff id="I36">West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK</nlm:aff></affiliation></author><author><name sortKey="Cook, Jackie" sort="Cook, Jackie" uniqKey="Cook J" first="Jackie" last="Cook">Jackie Cook</name><affiliation><nlm:aff id="I37">Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK</nlm:aff></affiliation></author><author><name sortKey="Paterson, Joan" sort="Paterson, Joan" uniqKey="Paterson J" first="Joan" last="Paterson">Joan Paterson</name><affiliation><nlm:aff id="I38">Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Douglas, Fiona" sort="Douglas, Fiona" uniqKey="Douglas F" first="Fiona" last="Douglas">Fiona Douglas</name><affiliation><nlm:aff id="I39">Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK</nlm:aff></affiliation></author><author><name sortKey="Brewer, Carole" sort="Brewer, Carole" uniqKey="Brewer C" first="Carole" last="Brewer">Carole Brewer</name><affiliation><nlm:aff id="I40">Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Hodgson, Shirley" sort="Hodgson, Shirley" uniqKey="Hodgson S" first="Shirley" last="Hodgson">Shirley Hodgson</name><affiliation><nlm:aff id="I41">Medical Genetics Unit, St George's, University of London, UK</nlm:aff></affiliation></author><author><name sortKey="Morrison, Patrick J" sort="Morrison, Patrick J" uniqKey="Morrison P" first="Patrick J" last="Morrison">Patrick J. Morrison</name><affiliation><nlm:aff id="I42">Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, and Department of Medical Genetics, Queens University Belfast, Belfast UK</nlm:aff></affiliation></author><author><name sortKey="Walker, Lisa" sort="Walker, Lisa" uniqKey="Walker L" first="Lisa" last="Walker">Lisa Walker</name><affiliation><nlm:aff id="I43">Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Rogers, Mark T" sort="Rogers, Mark T" uniqKey="Rogers M" first="Mark T" last="Rogers">Mark T. Rogers</name><affiliation><nlm:aff id="I44">All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK</nlm:aff></affiliation></author><author><name sortKey="Donaldson, Alan" sort="Donaldson, Alan" uniqKey="Donaldson A" first="Alan" last="Donaldson">Alan Donaldson</name><affiliation><nlm:aff id="I45">Clinical Genetics Department, St Michael's Hospital, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Dorkins, Huw" sort="Dorkins, Huw" uniqKey="Dorkins H" first="Huw" last="Dorkins">Huw Dorkins</name><affiliation><nlm:aff id="I46">North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, UK</nlm:aff></affiliation></author><author><name sortKey="Godwin, Andrew K" sort="Godwin, Andrew K" uniqKey="Godwin A" first="Andrew K" last="Godwin">Andrew K. Godwin</name><affiliation><nlm:aff id="I47">Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA</nlm:aff></affiliation></author><author><name sortKey="Bove, Betsy" sort="Bove, Betsy" uniqKey="Bove B" first="Betsy" last="Bove">Betsy Bove</name><affiliation><nlm:aff id="I48">Clinical Molecular Genetics Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Stoppa Lyonnet, Dominique" sort="Stoppa Lyonnet, Dominique" uniqKey="Stoppa Lyonnet D" first="Dominique" last="Stoppa-Lyonnet">Dominique Stoppa-Lyonnet</name><affiliation><nlm:aff id="I49">Service de Génétique Oncologique, Institut Curie, Paris, France, Unité INSERM U830, Institut Curie, Paris, France, Université Paris Descartes, Faculté de Médecine, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Houdayer, Claude" sort="Houdayer, Claude" uniqKey="Houdayer C" first="Claude" last="Houdayer">Claude Houdayer</name><affiliation><nlm:aff id="I50">Service de Génétique Oncologique, Institut Curie, Paris, France and Université Paris Descartes, Faculté de Pharmacie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Buecher, Bruno" sort="Buecher, Bruno" uniqKey="Buecher B" first="Bruno" last="Buecher">Bruno Buecher</name><affiliation><nlm:aff id="I51">Service de Génétique Oncologique, Institut Curie, 26 rue d'Ulm, Paris, France</nlm:aff></affiliation></author><author><name sortKey="De Pauw, Antoine" sort="De Pauw, Antoine" uniqKey="De Pauw A" first="Antoine" last="De Pauw">Antoine De Pauw</name><affiliation><nlm:aff id="I52">Service de Génétique Oncologique, Institut Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Mazoyer, Sylvie" sort="Mazoyer, Sylvie" uniqKey="Mazoyer S" first="Sylvie" last="Mazoyer">Sylvie Mazoyer</name><affiliation><nlm:aff id="I53">INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Calender, Alain" sort="Calender, Alain" uniqKey="Calender A" first="Alain" last="Calender">Alain Calender</name><affiliation><nlm:aff id="I54">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon Bérard, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Leone, Melanie" sort="Leone, Melanie" uniqKey="Leone M" first="Mélanie" last="Léoné">Mélanie Léoné</name><affiliation><nlm:aff id="I54">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon Bérard, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Bressac De Paillerets, Brigitte" sort="Bressac De Paillerets, Brigitte" uniqKey="Bressac De Paillerets B" first="Brigitte" last="Bressac- De Paillerets">Brigitte Bressac- De Paillerets</name><affiliation><nlm:aff id="I55">Service de Génétique, Institut de Cancérologie Gustave Roussy, Villejuif, France and INSERM U946, Fondation Jean Dausset, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Caron, Olivier" sort="Caron, Olivier" uniqKey="Caron O" first="Olivier" last="Caron">Olivier Caron</name><affiliation><nlm:aff id="I56">Consultation de Génétique, Département de Médecine, Institut de Cancérologie Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="Sobol, Hagay" sort="Sobol, Hagay" uniqKey="Sobol H" first="Hagay" last="Sobol">Hagay Sobol</name><affiliation><nlm:aff id="I57">Département Oncologie génétique, Prévention et Dépistage, INSERM CIC-P9502, Institut Paoli-Calmettes/Université d'Aix-Marseille II, Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Frenay, Marc" sort="Frenay, Marc" uniqKey="Frenay M" first="Marc" last="Frenay">Marc Frenay</name><affiliation><nlm:aff id="I58">Centre Antoine Lacassagne, Nice, France</nlm:aff></affiliation></author><author><name sortKey="Prieur, Fabienne" sort="Prieur, Fabienne" uniqKey="Prieur F" first="Fabienne" last="Prieur">Fabienne Prieur</name><affiliation><nlm:aff id="I59">Service de Génétique Clinique Chromosomique et Moléculaire, Centre Hospitalier Universitaire de St Etienne, St Etienne, France</nlm:aff></affiliation></author><author><name sortKey="Ferrer, Sandra Fert" sort="Ferrer, Sandra Fert" uniqKey="Ferrer S" first="Sandra Fert" last="Ferrer">Sandra Fert Ferrer</name><affiliation><nlm:aff id="I60">Laboratoire de Génétique Chromosomique, Hôtel Dieu Centre Hospitalier, BP 1125 Chambéry, France</nlm:aff></affiliation></author><author><name sortKey="Mortemousque, Isabelle" sort="Mortemousque, Isabelle" uniqKey="Mortemousque I" first="Isabelle" last="Mortemousque">Isabelle Mortemousque</name><affiliation><nlm:aff id="I61">Service de Génétique, Centre Hospitalier Universitaire Bretonneau, Tours, France</nlm:aff></affiliation></author><author><name sortKey="Buys, Saundra" sort="Buys, Saundra" uniqKey="Buys S" first="Saundra" last="Buys">Saundra Buys</name><affiliation><nlm:aff id="I63">Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA</nlm:aff></affiliation></author><author><name sortKey="Daly, Mary" sort="Daly, Mary" uniqKey="Daly M" first="Mary" last="Daly">Mary Daly</name><affiliation><nlm:aff id="I64">Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA</nlm:aff></affiliation></author><author><name sortKey="Miron, Alexander" sort="Miron, Alexander" uniqKey="Miron A" first="Alexander" last="Miron">Alexander Miron</name><affiliation><nlm:aff id="I65">Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Surgery, Harvard Medical School, 27 Drydock Avenue, Boston, MA 02210, USA</nlm:aff></affiliation></author><author><name sortKey="Terry, Mary Beth" sort="Terry, Mary Beth" uniqKey="Terry M" first="Mary Beth" last="Terry">Mary Beth Terry</name><affiliation><nlm:aff id="I66">Department of Epidemiology, Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L" last="Hopper">John L. Hopper</name><affiliation><nlm:aff id="I67">Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Melbourne School of Population Health, Level 1, 723 Swanston Street, The University of Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="John, Esther M" sort="John, Esther M" uniqKey="John E" first="Esther M" last="John">Esther M. John</name><affiliation><nlm:aff id="I68">Department of Epidemiology, Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538, USA</nlm:aff></affiliation></author><author><name sortKey="Southey, Melissa" sort="Southey, Melissa" uniqKey="Southey M" first="Melissa" last="Southey">Melissa Southey</name><affiliation><nlm:aff id="I69">Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Goldgar, David" sort="Goldgar, David" uniqKey="Goldgar D" first="David" last="Goldgar">David Goldgar</name><affiliation><nlm:aff id="I70">Department of Dermatology, University of Utah School of Medicine, 30 North 1900 East, SOM 4B454, Salt Lake City, UT 84132, USA</nlm:aff></affiliation></author><author><name sortKey="Singer, Christian F" sort="Singer, Christian F" uniqKey="Singer C" first="Christian F" last="Singer">Christian F. Singer</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Fink Retter, Anneliese" sort="Fink Retter, Anneliese" uniqKey="Fink Retter A" first="Anneliese" last="Fink-Retter">Anneliese Fink-Retter</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Tea, Muy Kheng" sort="Tea, Muy Kheng" uniqKey="Tea M" first="Muy-Kheng" last="Tea">Muy-Kheng Tea</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Kaulich, Daphne Geschwantler" sort="Kaulich, Daphne Geschwantler" uniqKey="Kaulich D" first="Daphne Geschwantler" last="Kaulich">Daphne Geschwantler Kaulich</name><affiliation><nlm:aff id="I71">Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Hansen, Thomas Vo" sort="Hansen, Thomas Vo" uniqKey="Hansen T" first="Thomas Vo" last="Hansen">Thomas Vo Hansen</name><affiliation><nlm:aff id="I72">Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Nielsen, Finn C" sort="Nielsen, Finn C" uniqKey="Nielsen F" first="Finn C" last="Nielsen">Finn C. Nielsen</name><affiliation><nlm:aff id="I72">Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Barkardottir, Rosa B" sort="Barkardottir, Rosa B" uniqKey="Barkardottir R" first="Rosa B" last="Barkardottir">Rosa B. Barkardottir</name><affiliation><nlm:aff id="I73">Department of Pathology, Landspitali - University Hospital, Reykjavik Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Gaudet, Mia" sort="Gaudet, Mia" uniqKey="Gaudet M" first="Mia" last="Gaudet">Mia Gaudet</name><affiliation><nlm:aff id="I74">Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Kirchhoff, Tomas" sort="Kirchhoff, Tomas" uniqKey="Kirchhoff T" first="Tomas" last="Kirchhoff">Tomas Kirchhoff</name><affiliation><nlm:aff id="I75">Department of Environmental Medicine, NYU Cancer Institute, New York University School of Medicine, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Joseph, Vijai" sort="Joseph, Vijai" uniqKey="Joseph V" first="Vijai" last="Joseph">Vijai Joseph</name><affiliation><nlm:aff id="I76">Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Dutra Clarke, Ana" sort="Dutra Clarke, Ana" uniqKey="Dutra Clarke A" first="Ana" last="Dutra-Clarke">Ana Dutra-Clarke</name><affiliation><nlm:aff id="I76">Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Offit, Kenneth" sort="Offit, Kenneth" uniqKey="Offit K" first="Kenneth" last="Offit">Kenneth Offit</name><affiliation><nlm:aff id="I76">Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Piedmonte, Marion" sort="Piedmonte, Marion" uniqKey="Piedmonte M" first="Marion" last="Piedmonte">Marion Piedmonte</name><affiliation><nlm:aff id="I77">Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Kirk, Judy" sort="Kirk, Judy" uniqKey="Kirk J" first="Judy" last="Kirk">Judy Kirk</name><affiliation><nlm:aff id="I78">Australia New Zealand (ANZGOG), Westmead Hospital, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Cohn, David" sort="Cohn, David" uniqKey="Cohn D" first="David" last="Cohn">David Cohn</name><affiliation><nlm:aff id="I79">Ohio State University, Columbus Cancer Council, Columbus, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Hurteau, Jean" sort="Hurteau, Jean" uniqKey="Hurteau J" first="Jean" last="Hurteau">Jean Hurteau</name><affiliation><nlm:aff id="I80">Evanston CCOP - NorthShore University Health System; University of Chicago, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Byron, John" sort="Byron, John" uniqKey="Byron J" first="John" last="Byron">John Byron</name><affiliation><nlm:aff id="I81">Southern Pines Women's Health Center, P.C., University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Fiorica, James" sort="Fiorica, James" uniqKey="Fiorica J" first="James" last="Fiorica">James Fiorica</name><affiliation><nlm:aff id="I82">Sarasota Memorial Healthcare, Tufts Medical Center, Sarasota, Florida, USA</nlm:aff></affiliation></author><author><name sortKey="Toland, Amanda E" sort="Toland, Amanda E" uniqKey="Toland A" first="Amanda E" last="Toland">Amanda E. Toland</name><affiliation><nlm:aff id="I83">Department of Molecular Virology, Immunology and Medical Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA</nlm:aff></affiliation></author><author><name sortKey="Montagna, Marco" sort="Montagna, Marco" uniqKey="Montagna M" first="Marco" last="Montagna">Marco Montagna</name><affiliation><nlm:aff id="I84">Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy</nlm:aff></affiliation></author><author><name sortKey="Oliani, Cristina" sort="Oliani, Cristina" uniqKey="Oliani C" first="Cristina" last="Oliani">Cristina Oliani</name><affiliation><nlm:aff id="I85">U.O.C. di Oncologia, ULSS5 Ovest Vicentino, Italy</nlm:aff></affiliation></author><author><name sortKey="Imyanitov, Evgeny" sort="Imyanitov, Evgeny" uniqKey="Imyanitov E" first="Evgeny" last="Imyanitov">Evgeny Imyanitov</name><affiliation><nlm:aff id="I86">Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, St.-Petersburg, Russia</nlm:aff></affiliation></author><author><name sortKey="Isaacs, Claudine" sort="Isaacs, Claudine" uniqKey="Isaacs C" first="Claudine" last="Isaacs">Claudine Isaacs</name><affiliation><nlm:aff id="I87">Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA</nlm:aff></affiliation></author><author><name sortKey="Tihomirova, Laima" sort="Tihomirova, Laima" uniqKey="Tihomirova L" first="Laima" last="Tihomirova">Laima Tihomirova</name><affiliation><nlm:aff id="I88">Latvian Biomedical Research and Study Centre, Latvia</nlm:aff></affiliation></author><author><name sortKey="Blanco, Ignacio" sort="Blanco, Ignacio" uniqKey="Blanco I" first="Ignacio" last="Blanco">Ignacio Blanco</name><affiliation><nlm:aff id="I89">Genetic Counselling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Lazaro, Conxi" sort="Lazaro, Conxi" uniqKey="Lazaro C" first="Conxi" last="Lazaro">Conxi Lazaro</name><affiliation><nlm:aff id="I90">Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Teule, Alex" sort="Teule, Alex" uniqKey="Teule A" first="Alex" last="Teulé">Alex Teulé</name><affiliation><nlm:aff id="I89">Genetic Counselling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Valle, J Del" sort="Valle, J Del" uniqKey="Valle J" first="J Del" last="Valle">J Del Valle</name><affiliation><nlm:aff id="I90">Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A" last="Gayther">Simon A. Gayther</name><affiliation><nlm:aff id="I91">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Odunsi, Kunle" sort="Odunsi, Kunle" uniqKey="Odunsi K" first="Kunle" last="Odunsi">Kunle Odunsi</name><affiliation><nlm:aff id="I92">Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Gross, Jenny" sort="Gross, Jenny" uniqKey="Gross J" first="Jenny" last="Gross">Jenny Gross</name><affiliation><nlm:aff id="I93">Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Karlan, Beth Y" sort="Karlan, Beth Y" uniqKey="Karlan B" first="Beth Y" last="Karlan">Beth Y. Karlan</name><affiliation><nlm:aff id="I93">Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Olah, Edith" sort="Olah, Edith" uniqKey="Olah E" first="Edith" last="Olah">Edith Olah</name><affiliation><nlm:aff id="I94">Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary</nlm:aff></affiliation></author><author><name sortKey="Teo, Soo Hwang" sort="Teo, Soo Hwang" uniqKey="Teo S" first="Soo-Hwang" last="Teo">Soo-Hwang Teo</name><affiliation><nlm:aff id="I95">Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Malaysia and University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Ganz, Patricia A" sort="Ganz, Patricia A" uniqKey="Ganz P" first="Patricia A" last="Ganz">Patricia A. Ganz</name><affiliation><nlm:aff id="I96">Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Beattie, Mary S" sort="Beattie, Mary S" uniqKey="Beattie M" first="Mary S" last="Beattie">Mary S. Beattie</name><affiliation><nlm:aff id="I97">UCSF Cancer Risk Program, University of California, San Francisco, CA; UCSF Departments of Medicine, Epidemiology, and Biostatistics, Sand Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Dorfling, Cecelia M" sort="Dorfling, Cecelia M" uniqKey="Dorfling C" first="Cecelia M" last="Dorfling">Cecelia M. Dorfling</name><affiliation><nlm:aff id="I98">Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, South Africa</nlm:aff></affiliation></author><author><name sortKey="Van Rensburg, Elizabeth Jansen" sort="Van Rensburg, Elizabeth Jansen" uniqKey="Van Rensburg E" first="Elizabeth Jansen" last="Van Rensburg">Elizabeth Jansen Van Rensburg</name><affiliation><nlm:aff id="I98">Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, South Africa</nlm:aff></affiliation></author><author><name sortKey="Diez, Orland" sort="Diez, Orland" uniqKey="Diez O" first="Orland" last="Diez">Orland Diez</name><affiliation><nlm:aff id="I99">Oncogenetics Laboratory. Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital. Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Kwong, Ava" sort="Kwong, Ava" uniqKey="Kwong A" first="Ava" last="Kwong">Ava Kwong</name><affiliation><nlm:aff id="I100">The Hong Kong Hereditary Breast Cancer Family Registry; The Universtiy of Hong Kong; Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong</nlm:aff></affiliation></author><author><name sortKey="Schmutzler, Rita K" sort="Schmutzler, Rita K" uniqKey="Schmutzler R" first="Rita K" last="Schmutzler">Rita K. Schmutzler</name><affiliation><nlm:aff id="I101">Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), University hospital of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Wappenschmidt, Barbara" sort="Wappenschmidt, Barbara" uniqKey="Wappenschmidt B" first="Barbara" last="Wappenschmidt">Barbara Wappenschmidt</name><affiliation><nlm:aff id="I101">Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), University hospital of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Engel, Christoph" sort="Engel, Christoph" uniqKey="Engel C" first="Christoph" last="Engel">Christoph Engel</name><affiliation><nlm:aff id="I102">Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany</nlm:aff></affiliation></author><author><name sortKey="Meindl, Alfons" sort="Meindl, Alfons" uniqKey="Meindl A" first="Alfons" last="Meindl">Alfons Meindl</name><affiliation><nlm:aff id="I103">Department of Gynaecology and Obstetrics, Division of Tumour Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Ditsch, Nina" sort="Ditsch, Nina" uniqKey="Ditsch N" first="Nina" last="Ditsch">Nina Ditsch</name><affiliation><nlm:aff id="I104">Department of Gynaecology and Obstetrics, Ludwig-Maximilian University Munich, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Arnold, Norbert" sort="Arnold, Norbert" uniqKey="Arnold N" first="Norbert" last="Arnold">Norbert Arnold</name><affiliation><nlm:aff id="I105">Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Heidemann, Simone" sort="Heidemann, Simone" uniqKey="Heidemann S" first="Simone" last="Heidemann">Simone Heidemann</name><affiliation><nlm:aff id="I106">Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Niederacher, Dieter" sort="Niederacher, Dieter" uniqKey="Niederacher D" first="Dieter" last="Niederacher">Dieter Niederacher</name><affiliation><nlm:aff id="I107">Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany</nlm:aff></affiliation></author><author><name sortKey="Preisler Adams, Sabine" sort="Preisler Adams, Sabine" uniqKey="Preisler Adams S" first="Sabine" last="Preisler-Adams">Sabine Preisler-Adams</name><affiliation><nlm:aff id="I108">Institute of Human Genetics, University of Münster, Münster, Germany</nlm:aff></affiliation></author><author><name sortKey="Gadzicki, Dorothea" sort="Gadzicki, Dorothea" uniqKey="Gadzicki D" first="Dorothea" last="Gadzicki">Dorothea Gadzicki</name><affiliation><nlm:aff id="I109">Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany</nlm:aff></affiliation></author><author><name sortKey="Varon Mateeva, Raymonda" sort="Varon Mateeva, Raymonda" uniqKey="Varon Mateeva R" first="Raymonda" last="Varon-Mateeva">Raymonda Varon-Mateeva</name><affiliation><nlm:aff id="I110">Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin, Germany</nlm:aff></affiliation></author><author><name sortKey="Deissler, Helmut" sort="Deissler, Helmut" uniqKey="Deissler H" first="Helmut" last="Deissler">Helmut Deissler</name><affiliation><nlm:aff id="I111">Department of Gynaecology and Obstetrics, University Hospital Ulm, Germany</nlm:aff></affiliation></author><author><name sortKey="Gehrig, Andrea" sort="Gehrig, Andrea" uniqKey="Gehrig A" first="Andrea" last="Gehrig">Andrea Gehrig</name><affiliation><nlm:aff id="I112">Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Sutter, Christian" sort="Sutter, Christian" uniqKey="Sutter C" first="Christian" last="Sutter">Christian Sutter</name><affiliation><nlm:aff id="I113">Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Kast, Karin" sort="Kast, Karin" uniqKey="Kast K" first="Karin" last="Kast">Karin Kast</name><affiliation><nlm:aff id="I114">Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University. Dresden, Germany</nlm:aff></affiliation></author><author><name sortKey="Fiebig, Britta" sort="Fiebig, Britta" uniqKey="Fiebig B" first="Britta" last="Fiebig">Britta Fiebig</name><affiliation><nlm:aff id="I115">Institute of Human Genetics, University Regensburg, Regensbirg. Germany</nlm:aff></affiliation></author><author><name sortKey="Sch Fer, Dieter" sort="Sch Fer, Dieter" uniqKey="Sch Fer D" first="Dieter" last="Sch Fer">Dieter Sch Fer</name><affiliation><nlm:aff id="I116">Institute of Human Genetics, University Hospital Frankfurt a.M., Germany Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Caldes, Trinidad" sort="Caldes, Trinidad" uniqKey="Caldes T" first="Trinidad" last="Caldes">Trinidad Caldes</name><affiliation><nlm:aff id="I117">Molecular Oncology Laboratory, Hospital Clinico San Carlos, Martin Lagos s/n, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="De La Hoya, Miguel" sort="De La Hoya, Miguel" uniqKey="De La Hoya M" first="Miguel" last="De La Hoya">Miguel De La Hoya</name><affiliation><nlm:aff id="I117">Molecular Oncology Laboratory, Hospital Clinico San Carlos, Martin Lagos s/n, Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name><affiliation><nlm:aff id="I118">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. BOX 700, 00029 HUS, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Muranen, Taru A" sort="Muranen, Taru A" uniqKey="Muranen T" first="Taru A" last="Muranen">Taru A. Muranen</name><affiliation><nlm:aff id="I118">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. BOX 700, 00029 HUS, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Lesperance, Bernard" sort="Lesperance, Bernard" uniqKey="Lesperance B" first="Bernard" last="Lespérance">Bernard Lespérance</name><affiliation><nlm:aff id="I119">Faculty of Medicine - Medicine and Medical Specialties, Université de Montréal Hemato-oncology service, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin Blvd West Montreal, QC, Canada</nlm:aff></affiliation></author><author><name sortKey="Spurdle, Amanda B" sort="Spurdle, Amanda B" uniqKey="Spurdle A" first="Amanda B" last="Spurdle">Amanda B. Spurdle</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Neuhausen, Susan L" sort="Neuhausen, Susan L" uniqKey="Neuhausen S" first="Susan L" last="Neuhausen">Susan L. Neuhausen</name><affiliation><nlm:aff id="I121">Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ding, Yuan C" sort="Ding, Yuan C" uniqKey="Ding Y" first="Yuan C" last="Ding">Yuan C. Ding</name><affiliation><nlm:aff id="I121">Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Xianshu" sort="Wang, Xianshu" uniqKey="Wang X" first="Xianshu" last="Wang">Xianshu Wang</name><affiliation><nlm:aff id="I122">Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Fredericksen, Zachary" sort="Fredericksen, Zachary" uniqKey="Fredericksen Z" first="Zachary" last="Fredericksen">Zachary Fredericksen</name><affiliation><nlm:aff id="I123">Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Pankratz, Vernon S" sort="Pankratz, Vernon S" uniqKey="Pankratz V" first="Vernon S" last="Pankratz">Vernon S. Pankratz</name><affiliation><nlm:aff id="I123">Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Lindor, Noralane M" sort="Lindor, Noralane M" uniqKey="Lindor N" first="Noralane M" last="Lindor">Noralane M. Lindor</name><affiliation><nlm:aff id="I124">Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Peterlongo, Paolo" sort="Peterlongo, Paolo" uniqKey="Peterlongo P" first="Paolo" last="Peterlongo">Paolo Peterlongo</name><affiliation><nlm:aff id="I125">Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Manoukian, Siranoush" sort="Manoukian, Siranoush" uniqKey="Manoukian S" first="Siranoush" last="Manoukian">Siranoush Manoukian</name><affiliation><nlm:aff id="I126">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Peissel, Bernard" sort="Peissel, Bernard" uniqKey="Peissel B" first="Bernard" last="Peissel">Bernard Peissel</name><affiliation><nlm:aff id="I126">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Zaffaroni, Daniela" sort="Zaffaroni, Daniela" uniqKey="Zaffaroni D" first="Daniela" last="Zaffaroni">Daniela Zaffaroni</name><affiliation><nlm:aff id="I126">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Bonanni, Bernardo" sort="Bonanni, Bernardo" uniqKey="Bonanni B" first="Bernardo" last="Bonanni">Bernardo Bonanni</name><affiliation><nlm:aff id="I127">Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan Italy</nlm:aff></affiliation></author><author><name sortKey="Bernard, Loris" sort="Bernard, Loris" uniqKey="Bernard L" first="Loris" last="Bernard">Loris Bernard</name><affiliation><nlm:aff id="I128">Department of Experimental Oncology, Istituto Europeo di Oncologia, Milan, Italy and Consortium for Genomics Technology (Cogentech), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Dolcetti, Riccardo" sort="Dolcetti, Riccardo" uniqKey="Dolcetti R" first="Riccardo" last="Dolcetti">Riccardo Dolcetti</name><affiliation><nlm:aff id="I129">Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy</nlm:aff></affiliation></author><author><name sortKey="Papi, Laura" sort="Papi, Laura" uniqKey="Papi L" first="Laura" last="Papi">Laura Papi</name><affiliation><nlm:aff id="I130">Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Firenze, Italy</nlm:aff></affiliation></author><author><name sortKey="Ottini, Laura" sort="Ottini, Laura" uniqKey="Ottini L" first="Laura" last="Ottini">Laura Ottini</name><affiliation><nlm:aff id="I131">Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Radice, Paolo" sort="Radice, Paolo" uniqKey="Radice P" first="Paolo" last="Radice">Paolo Radice</name><affiliation><nlm:aff id="I125">Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Greene, Mark H" sort="Greene, Mark H" uniqKey="Greene M" first="Mark H" last="Greene">Mark H. Greene</name><affiliation><nlm:aff id="I132">Clinical Genetics Branch, DCEG, NCI; Room EPS 7032, Rockville, MD 20852, USA</nlm:aff></affiliation></author><author><name sortKey="Loud, Jennifer T" sort="Loud, Jennifer T" uniqKey="Loud J" first="Jennifer T" last="Loud">Jennifer T. Loud</name><affiliation><nlm:aff id="I132">Clinical Genetics Branch, DCEG, NCI; Room EPS 7032, Rockville, MD 20852, USA</nlm:aff></affiliation></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L" last="Andrulis">Irene L. Andrulis</name><affiliation><nlm:aff id="I133">Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON; Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Ozcelik, Hilmi" sort="Ozcelik, Hilmi" uniqKey="Ozcelik H" first="Hilmi" last="Ozcelik">Hilmi Ozcelik</name><affiliation><nlm:aff id="I134">Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Mulligan, Anna Marie" sort="Mulligan, Anna Marie" uniqKey="Mulligan A" first="Anna Marie" last="Mulligan">Anna Marie Mulligan</name><affiliation><nlm:aff id="I135">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine, and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name><affiliation><nlm:aff id="I136">Ontario Cancer Genetics Network: Cancer Care Ontario, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Thomassen, Mads" sort="Thomassen, Mads" uniqKey="Thomassen M" first="Mads" last="Thomassen">Mads Thomassen</name><affiliation><nlm:aff id="I137">Department of Clinical Genetics, Odense University Hospital, Denmark</nlm:aff></affiliation></author><author><name sortKey="Gerdes, Anne Marie" sort="Gerdes, Anne Marie" uniqKey="Gerdes A" first="Anne-Marie" last="Gerdes">Anne-Marie Gerdes</name><affiliation><nlm:aff id="I138">Department of Clincial Genetics, Rigshospital and Copenhagen University, Denmark</nlm:aff></affiliation></author><author><name sortKey="Jensen, Uffe B" sort="Jensen, Uffe B" uniqKey="Jensen U" first="Uffe B" last="Jensen">Uffe B. Jensen</name><affiliation><nlm:aff id="I139">Department of Clinical Genetics, Skejby Hospital, Aarhus, Denmark</nlm:aff></affiliation></author><author><name sortKey="Skytte, Anne Bine" sort="Skytte, Anne Bine" uniqKey="Skytte A" first="Anne-Bine" last="Skytte">Anne-Bine Skytte</name><affiliation><nlm:aff id="I140">Department of Clinical Genetics, Vejle Hospital, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kruse, Torben A" sort="Kruse, Torben A" uniqKey="Kruse T" first="Torben A" last="Kruse">Torben A. Kruse</name><affiliation><nlm:aff id="I137">Department of Clinical Genetics, Odense University Hospital, Denmark</nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name><affiliation><nlm:aff id="I3">Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J" last="Couch">Fergus J. Couch</name><affiliation><nlm:aff id="I141">Department of Laboratory Medicine and Pathology, and Health Sciences Research, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Simard, Jacques" sort="Simard, Jacques" uniqKey="Simard J" first="Jacques" last="Simard">Jacques Simard</name><affiliation><nlm:aff id="I142">Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, T3-57, Quebec City and Canada Research Chair in Oncogenetics, Department of Molecular Medicine, Faculty of Medicine, Laval University, QC, Canada</nlm:aff></affiliation></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F" last="Easton">Douglas F. Easton</name><affiliation><nlm:aff id="I1">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</nlm:aff></affiliation></author></analytic><series><title level="j">Breast Cancer Research : BCR</title><idno type="ISSN">1465-5411</idno><idno type="eISSN">1465-542X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Introduction</title><p>Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, <italic>CDKN2A/B)</italic>, rs10995190 (<italic>ZNF365)</italic>, rs704010 (<italic>ZMIZ1</italic>), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near <italic>PTHLH) </italic>and rs865686 (9q31.2).</p></sec><sec><title>Methods</title><p>To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>carriers, we genotyped these SNPs in 12,599 <italic>BRCA1 </italic>and 7,132 <italic>BRCA2 </italic>mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.</p></sec><sec><title>Results</title><p>Only SNP rs10771399 near <italic>PTHLH </italic>was associated with breast cancer risk for <italic>BRCA1 </italic>mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, <italic>P</italic>-trend = 3 × 10<sup>-4</sup>). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, <italic>P</italic>-trend = 3.1 × 10<sup>-5</sup>, <italic>P</italic>-difference = 0.03). Four SNPs were associated with the risk of breast cancer for <italic>BRCA2 </italic>mutation carriers: rs10995190, <italic>P</italic>-trend = 0.015; rs1011970, <italic>P</italic>-trend = 0.048; rs865686, 2df-<italic>P </italic>= 0.007; rs1292011 2df-<italic>P </italic>= 0.03. rs10771399 (<italic>PTHLH</italic>) was predominantly associated with estrogen receptor (ER)-negative breast cancer for <italic>BRCA1 </italic>mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, <italic>P</italic>-trend = 4 × 10<sup>-5</sup>) and there was marginal evidence of association with ER-negative breast cancer for <italic>BRCA2 </italic>mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, <italic>P</italic>-trend = 0.049).</p></sec><sec><title>Conclusions</title><p>The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Antoniou, A" uniqKey="Antoniou A">A Antoniou</name></author><author><name sortKey="Pharoah, Pd" uniqKey="Pharoah P">PD Pharoah</name></author><author><name sortKey="Narod, S" uniqKey="Narod S">S Narod</name></author><author><name sortKey="Risch, Ha" uniqKey="Risch H">HA Risch</name></author><author><name sortKey="Eyfjord, Je" uniqKey="Eyfjord J">JE Eyfjord</name></author><author><name sortKey="Hopper, Jl" uniqKey="Hopper J">JL Hopper</name></author><author><name sortKey="Loman, N" uniqKey="Loman N">N Loman</name></author><author><name sortKey="Olsson, H" uniqKey="Olsson H">H Olsson</name></author><author><name sortKey="Johannsson, O" uniqKey="Johannsson O">O Johannsson</name></author><author><name sortKey="Borg, A" uniqKey="Borg A">A Borg</name></author><author><name sortKey="Pasini, B" uniqKey="Pasini B">B Pasini</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Breast Cancer Res</journal-id><journal-id journal-id-type="iso-abbrev">Breast Cancer Res</journal-id><journal-title-group><journal-title>Breast Cancer Research : BCR</journal-title></journal-title-group><issn pub-type="ppub">1465-5411</issn><issn pub-type="epub">1465-542X</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22348646</article-id><article-id pub-id-type="pmc">3496151</article-id><article-id pub-id-type="publisher-id">bcr3121</article-id><article-id pub-id-type="doi">10.1186/bcr3121</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Common variants at 12p11, 12q24, 9p21, 9q31.2 and in <italic>ZNF365 </italic>are associated with breast cancer risk for <italic>BRCA1 </italic>and/or <italic>BRCA2 </italic>mutation 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id="A164"><name><surname>Papi</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="I130">130</xref><email>l.papi@dfc.unifi.it</email></contrib><contrib contrib-type="author" id="A165"><name><surname>Ottini</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="I131">131</xref><email>laura.ottini@uniroma1.it</email></contrib><contrib contrib-type="author" id="A166"><name><surname>Radice</surname><given-names>Paolo</given-names></name><xref ref-type="aff" rid="I125">125</xref><email>paolo.radice@ifom-ieo-campus.it</email></contrib><contrib contrib-type="author" id="A167"><name><surname>Greene</surname><given-names>Mark H</given-names></name><xref ref-type="aff" rid="I132">132</xref><email>greenem@mail.nih.gov</email></contrib><contrib contrib-type="author" id="A168"><name><surname>Loud</surname><given-names>Jennifer T</given-names></name><xref ref-type="aff" rid="I132">132</xref><email>loudj@mail.nih.gov</email></contrib><contrib contrib-type="author" id="A169"><name><surname>Andrulis</surname><given-names>Irene L</given-names></name><xref ref-type="aff" rid="I133">133</xref><email>andrulis@lunenfeld.ca</email></contrib><contrib contrib-type="author" id="A170"><name><surname>Ozcelik</surname><given-names>Hilmi</given-names></name><xref ref-type="aff" rid="I134">134</xref><email>ozcelik@lunenfeld.ca</email></contrib><contrib contrib-type="author" id="A171"><name><surname>Mulligan</surname><given-names>Anna Marie</given-names></name><xref ref-type="aff" rid="I135">135</xref><email>MulliganA@smh.toronto.on.ca</email></contrib><contrib contrib-type="author" id="A172"><name><surname>Glendon</surname><given-names>Gord</given-names></name><xref ref-type="aff" rid="I136">136</xref><email>gord.glendon@cancercare.on.ca</email></contrib><contrib contrib-type="author" id="A173"><name><surname>Thomassen</surname><given-names>Mads</given-names></name><xref ref-type="aff" rid="I137">137</xref><email>mads.thomassen@ouh.regionsyddanmark.dk</email></contrib><contrib contrib-type="author" id="A174"><name><surname>Gerdes</surname><given-names>Anne-Marie</given-names></name><xref ref-type="aff" rid="I138">138</xref><email>anne-marie.gerdes@rh.regionh.dk</email></contrib><contrib contrib-type="author" id="A175"><name><surname>Jensen</surname><given-names>Uffe B</given-names></name><xref ref-type="aff" rid="I139">139</xref><email>uffejens@rm.dk</email></contrib><contrib contrib-type="author" id="A176"><name><surname>Skytte</surname><given-names>Anne-Bine</given-names></name><xref ref-type="aff" rid="I140">140</xref><email>Anne-Bine.Skytte@slb.regionsyddanmark.dk</email></contrib><contrib contrib-type="author" id="A177"><name><surname>Kruse</surname><given-names>Torben A</given-names></name><xref ref-type="aff" rid="I137">137</xref><email>torben.kruse@ouh.regionsyddanmark.dk</email></contrib><contrib contrib-type="author" id="A178"><name><surname>Chenevix-Trench</surname><given-names>Georgia</given-names></name><xref ref-type="aff" rid="I3">3</xref><email>georgiaT@qimr.edu.au</email></contrib><contrib contrib-type="author" id="A179"><name><surname>Couch</surname><given-names>Fergus J</given-names></name><xref ref-type="aff" rid="I141">141</xref><email>Couch.fergus@mayo.edu</email></contrib><contrib contrib-type="author" id="A180"><name><surname>Simard</surname><given-names>Jacques</given-names></name><xref ref-type="aff" rid="I142">142</xref><email>Jacques.Simard@crchul.ulaval.ca</email></contrib><contrib contrib-type="author" id="A181"><name><surname>Easton</surname><given-names>Douglas F</given-names></name><xref ref-type="aff" rid="I1">1</xref><email>douglas@srl.cam.ac.uk</email></contrib><on-behalf-of>CIMBA, SWE-BRCA <xref ref-type="corresp" rid="d33e1579"></xref></on-behalf-of></contrib-group><contrib-group><on-behalf-of>HEBON <xref ref-type="corresp" rid="d33e1583"></xref></on-behalf-of></contrib-group><contrib-group><on-behalf-of>EMBRACE <xref ref-type="corresp" rid="d33e1587"></xref></on-behalf-of></contrib-group><contrib-group><on-behalf-of>GEMO Collaborators Study <xref ref-type="corresp" rid="d33e1591"></xref></on-behalf-of></contrib-group><contrib-group><on-behalf-of>kConFab Investigators <xref ref-type="corresp" rid="d33e1595"></xref></on-behalf-of></contrib-group><aff id="I1"><label>1</label>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK</aff><aff id="I2"><label>2</label>Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, T3-57, Quebec City, QC Canada</aff><aff id="I3"><label>3</label>Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, QLD 4006, Australia</aff><aff id="I4"><label>4</label>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, 28 rue Laënnec, Lyon 69373, France and INSERM U1052, CNRS UMR5286, Université Lyon 1, Cancer Research Center of Lyon, 28 rue Laënnec, Lyon 69373, France</aff><aff id="I5"><label>5</label>Section of Genetic Oncology, Dept. of Laboratory Medicine, University and University Hospital of Pisa, Via Roma 57, 56125 Pisa, Italy</aff><aff id="I6"><label>6</label>Department of Oncology, Lund University Hospital, Lund, Sweden</aff><aff id="I7"><label>7</label>Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden</aff><aff id="I8"><label>8</label>Department of Oncology, Karolinska University Hospital, Stockholm, Sweden</aff><aff id="I9"><label>9</label>Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</aff><aff id="I10"><label>10</label>Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden</aff><aff id="I11"><label>11</label>Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</aff><aff id="I12"><label>12</label>Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland</aff><aff id="I13"><label>13</label>Department of Genetics and Pathology, Pomeranian Medical University, Szczecin and Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland</aff><aff id="I14"><label>14</label>Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain and Spanish Network on Rare Diseases (CIBERER)</aff><aff id="I15"><label>15</label>Institute of Biology and Molecular Genetics. Universidad de Valladolid (IBGM-UVA), Valladolid, Spain</aff><aff id="I16"><label>16</label>Oncology unit. Hospital clinico Universitario "Lozano Blesa", Zaragoza, Spain</aff><aff id="I17"><label>17</label>Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain and Spanish Network on Rare Diseases (CIBERER)</aff><aff id="I18"><label>18</label>Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany</aff><aff id="I19"><label>19</label>Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands</aff><aff id="I20"><label>20</label>Department of Clinical Genetics, Academic Meical Center, Amsterdam, The Netherlands</aff><aff id="I21"><label>21</label>Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands</aff><aff id="I22"><label>22</label>Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands</aff><aff id="I23"><label>23</label>Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands</aff><aff id="I24"><label>24</label>Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands</aff><aff id="I25"><label>25</label>Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands</aff><aff id="I26"><label>26</label>Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands</aff><aff id="I27"><label>27</label>Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands</aff><aff id="I28"><label>28</label>Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands</aff><aff id="I29"><label>29</label>Department of Genetics, University Medical Center, Groningen University, Groningen, The Netherlands</aff><aff id="I30"><label>30</label>Netherlands Cancer Institute, Amsterdam, The Netherlands</aff><aff id="I31"><label>31</label>Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</aff><aff id="I32"><label>32</label>Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK</aff><aff id="I33"><label>33</label>Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, UK</aff><aff id="I34"><label>34</label>Yorkshire Regional Genetics Service, Leeds, UK</aff><aff id="I35"><label>35</label>Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK</aff><aff id="I36"><label>36</label>West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK</aff><aff id="I37"><label>37</label>Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK</aff><aff id="I38"><label>38</label>Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK</aff><aff id="I39"><label>39</label>Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK</aff><aff id="I40"><label>40</label>Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK</aff><aff id="I41"><label>41</label>Medical Genetics Unit, St George's, University of London, UK</aff><aff id="I42"><label>42</label>Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, and Department of Medical Genetics, Queens University Belfast, Belfast UK</aff><aff id="I43"><label>43</label>Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK</aff><aff id="I44"><label>44</label>All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK</aff><aff id="I45"><label>45</label>Clinical Genetics Department, St Michael's Hospital, Bristol, UK</aff><aff id="I46"><label>46</label>North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, UK</aff><aff id="I47"><label>47</label>Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA</aff><aff id="I48"><label>48</label>Clinical Molecular Genetics Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA</aff><aff id="I49"><label>49</label>Service de Génétique Oncologique, Institut Curie, Paris, France, Unité INSERM U830, Institut Curie, Paris, France, Université Paris Descartes, Faculté de Médecine, Paris, France</aff><aff id="I50"><label>50</label>Service de Génétique Oncologique, Institut Curie, Paris, France and Université Paris Descartes, Faculté de Pharmacie, Paris, France</aff><aff id="I51"><label>51</label>Service de Génétique Oncologique, Institut Curie, 26 rue d'Ulm, Paris, France</aff><aff id="I52"><label>52</label>Service de Génétique Oncologique, Institut Curie, Paris, France</aff><aff id="I53"><label>53</label>INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France</aff><aff id="I54"><label>54</label>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon Bérard, Lyon, France</aff><aff id="I55"><label>55</label>Service de Génétique, Institut de Cancérologie Gustave Roussy, Villejuif, France and INSERM U946, Fondation Jean Dausset, Paris, France</aff><aff id="I56"><label>56</label>Consultation de Génétique, Département de Médecine, Institut de Cancérologie Gustave Roussy, Villejuif, France</aff><aff id="I57"><label>57</label>Département Oncologie génétique, Prévention et Dépistage, INSERM CIC-P9502, Institut Paoli-Calmettes/Université d'Aix-Marseille II, Marseille, France</aff><aff id="I58"><label>58</label>Centre Antoine Lacassagne, Nice, France</aff><aff id="I59"><label>59</label>Service de Génétique Clinique Chromosomique et Moléculaire, Centre Hospitalier Universitaire de St Etienne, St Etienne, France</aff><aff id="I60"><label>60</label>Laboratoire de Génétique Chromosomique, Hôtel Dieu Centre Hospitalier, BP 1125 Chambéry, France</aff><aff id="I61"><label>61</label>Service de Génétique, Centre Hospitalier Universitaire Bretonneau, Tours, France</aff><aff id="I62"><label>62</label>Cancer Genetics Network "Groupe Génétique et Cancer", Fédération Nationale des Centres de Lutte Contre le Cancer, France</aff><aff id="I63"><label>63</label>Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA</aff><aff id="I64"><label>64</label>Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA</aff><aff id="I65"><label>65</label>Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Surgery, Harvard Medical School, 27 Drydock Avenue, Boston, MA 02210, USA</aff><aff id="I66"><label>66</label>Department of Epidemiology, Columbia University, New York, NY, USA</aff><aff id="I67"><label>67</label>Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Melbourne School of Population Health, Level 1, 723 Swanston Street, The University of Melbourne, VIC 3010, Australia</aff><aff id="I68"><label>68</label>Department of Epidemiology, Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA 94538, USA</aff><aff id="I69"><label>69</label>Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Australia</aff><aff id="I70"><label>70</label>Department of Dermatology, University of Utah School of Medicine, 30 North 1900 East, SOM 4B454, Salt Lake City, UT 84132, USA</aff><aff id="I71"><label>71</label>Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria</aff><aff id="I72"><label>72</label>Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark</aff><aff id="I73"><label>73</label>Department of Pathology, Landspitali - University Hospital, Reykjavik Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland</aff><aff id="I74"><label>74</label>Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA</aff><aff id="I75"><label>75</label>Department of Environmental Medicine, NYU Cancer Institute, New York University School of Medicine, New York, NY, USA</aff><aff id="I76"><label>76</label>Clinical Cancer Genetics Laboratory, Memorial Sloane Kettering Cancer Center, New York, NY, USA</aff><aff id="I77"><label>77</label>Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA</aff><aff id="I78"><label>78</label>Australia New Zealand (ANZGOG), Westmead Hospital, Sydney, Australia</aff><aff id="I79"><label>79</label>Ohio State University, Columbus Cancer Council, Columbus, OH, USA</aff><aff id="I80"><label>80</label>Evanston CCOP - NorthShore University Health System; University of Chicago, Chicago, IL, USA</aff><aff id="I81"><label>81</label>Southern Pines Women's Health Center, P.C., University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</aff><aff id="I82"><label>82</label>Sarasota Memorial Healthcare, Tufts Medical Center, Sarasota, Florida, USA</aff><aff id="I83"><label>83</label>Department of Molecular Virology, Immunology and Medical Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA</aff><aff id="I84"><label>84</label>Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy</aff><aff id="I85"><label>85</label>U.O.C. di Oncologia, ULSS5 Ovest Vicentino, Italy</aff><aff id="I86"><label>86</label>Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, St.-Petersburg, Russia</aff><aff id="I87"><label>87</label>Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA</aff><aff id="I88"><label>88</label>Latvian Biomedical Research and Study Centre, Latvia</aff><aff id="I89"><label>89</label>Genetic Counselling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</aff><aff id="I90"><label>90</label>Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain</aff><aff id="I91"><label>91</label>Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</aff><aff id="I92"><label>92</label>Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA</aff><aff id="I93"><label>93</label>Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA</aff><aff id="I94"><label>94</label>Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary</aff><aff id="I95"><label>95</label>Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Malaysia and University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia</aff><aff id="I96"><label>96</label>Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA</aff><aff id="I97"><label>97</label>UCSF Cancer Risk Program, University of California, San Francisco, CA; UCSF Departments of Medicine, Epidemiology, and Biostatistics, Sand Francisco, CA, USA</aff><aff id="I98"><label>98</label>Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, South Africa</aff><aff id="I99"><label>99</label>Oncogenetics Laboratory. Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital. Barcelona, Spain</aff><aff id="I100"><label>100</label>The Hong Kong Hereditary Breast Cancer Family Registry; The Universtiy of Hong Kong; Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong</aff><aff id="I101"><label>101</label>Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), University hospital of Cologne, Cologne, Germany</aff><aff id="I102"><label>102</label>Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany</aff><aff id="I103"><label>103</label>Department of Gynaecology and Obstetrics, Division of Tumour Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany</aff><aff id="I104"><label>104</label>Department of Gynaecology and Obstetrics, Ludwig-Maximilian University Munich, Munich, Germany</aff><aff id="I105"><label>105</label>Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany</aff><aff id="I106"><label>106</label>Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany</aff><aff id="I107"><label>107</label>Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany</aff><aff id="I108"><label>108</label>Institute of Human Genetics, University of Münster, Münster, Germany</aff><aff id="I109"><label>109</label>Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany</aff><aff id="I110"><label>110</label>Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin, Germany</aff><aff id="I111"><label>111</label>Department of Gynaecology and Obstetrics, University Hospital Ulm, Germany</aff><aff id="I112"><label>112</label>Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany</aff><aff id="I113"><label>113</label>Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Germany</aff><aff id="I114"><label>114</label>Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University. Dresden, Germany</aff><aff id="I115"><label>115</label>Institute of Human Genetics, University Regensburg, Regensbirg. Germany</aff><aff id="I116"><label>116</label>Institute of Human Genetics, University Hospital Frankfurt a.M., Germany Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain</aff><aff id="I117"><label>117</label>Molecular Oncology Laboratory, Hospital Clinico San Carlos, Martin Lagos s/n, Madrid, Spain</aff><aff id="I118"><label>118</label>Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. BOX 700, 00029 HUS, Helsinki, Finland</aff><aff id="I119"><label>119</label>Faculty of Medicine - Medicine and Medical Specialties, Université de Montréal Hemato-oncology service, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin Blvd West Montreal, QC, Canada</aff><aff id="I120"><label>120</label>Peter MacCallum Cancer Center, Melbourne, VIC, Australia</aff><aff id="I121"><label>121</label>Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA</aff><aff id="I122"><label>122</label>Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA</aff><aff id="I123"><label>123</label>Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA</aff><aff id="I124"><label>124</label>Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA</aff><aff id="I125"><label>125</label>Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy</aff><aff id="I126"><label>126</label>Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Milan, Italy</aff><aff id="I127"><label>127</label>Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan Italy</aff><aff id="I128"><label>128</label>Department of Experimental Oncology, Istituto Europeo di Oncologia, Milan, Italy and Consortium for Genomics Technology (Cogentech), Milan, Italy</aff><aff id="I129"><label>129</label>Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy</aff><aff id="I130"><label>130</label>Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Firenze, Italy</aff><aff id="I131"><label>131</label>Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy</aff><aff id="I132"><label>132</label>Clinical Genetics Branch, DCEG, NCI; Room EPS 7032, Rockville, MD 20852, USA</aff><aff id="I133"><label>133</label>Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON; Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada</aff><aff id="I134"><label>134</label>Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada</aff><aff id="I135"><label>135</label>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine, and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada</aff><aff id="I136"><label>136</label>Ontario Cancer Genetics Network: Cancer Care Ontario, Toronto, ON, Canada</aff><aff id="I137"><label>137</label>Department of Clinical Genetics, Odense University Hospital, Denmark</aff><aff id="I138"><label>138</label>Department of Clincial Genetics, Rigshospital and Copenhagen University, Denmark</aff><aff id="I139"><label>139</label>Department of Clinical Genetics, Skejby Hospital, Aarhus, Denmark</aff><aff id="I140"><label>140</label>Department of Clinical Genetics, Vejle Hospital, Denmark</aff><aff id="I141"><label>141</label>Department of Laboratory Medicine and Pathology, and Health Sciences Research, Mayo Clinic, Rochester, MN, USA</aff><aff id="I142"><label>142</label>Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, T3-57, Quebec City and Canada Research Chair in Oncogenetics, Department of Molecular Medicine, Faculty of Medicine, Laval University, QC, Canada</aff><author-notes><corresp id="d33e1579">CIMBA, SWE-BRCA </corresp><corresp id="d33e1583">HEBON </corresp><corresp id="d33e1587">EMBRACE </corresp><corresp id="d33e1591">GEMO Collaborators Study </corresp><corresp id="d33e1595">kConFab Investigators </corresp></author-notes><pub-date pub-type="ppub"><year>2012</year></pub-date><pub-date pub-type="epub"><day>20</day><month>2</month><year>2012</year></pub-date><volume>14</volume><issue>1</issue><fpage>R33</fpage><lpage>R33</lpage><history><date date-type="received"><day>21</day><month>9</month><year>2011</year></date><date date-type="rev-recd"><day>15</day><month>11</month><year>2011</year></date><date date-type="accepted"><day>20</day><month>2</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012 Antoniou et al.; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>Antoniou et al.; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri xlink:href="http://breast-cancer-research.com/content/14/1/R33"></self-uri><abstract><sec><title>Introduction</title><p>Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, <italic>CDKN2A/B)</italic>, rs10995190 (<italic>ZNF365)</italic>, rs704010 (<italic>ZMIZ1</italic>), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near <italic>PTHLH) </italic>and rs865686 (9q31.2).</p></sec><sec><title>Methods</title><p>To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>carriers, we genotyped these SNPs in 12,599 <italic>BRCA1 </italic>and 7,132 <italic>BRCA2 </italic>mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.</p></sec><sec><title>Results</title><p>Only SNP rs10771399 near <italic>PTHLH </italic>was associated with breast cancer risk for <italic>BRCA1 </italic>mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, <italic>P</italic>-trend = 3 × 10<sup>-4</sup>). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, <italic>P</italic>-trend = 3.1 × 10<sup>-5</sup>, <italic>P</italic>-difference = 0.03). Four SNPs were associated with the risk of breast cancer for <italic>BRCA2 </italic>mutation carriers: rs10995190, <italic>P</italic>-trend = 0.015; rs1011970, <italic>P</italic>-trend = 0.048; rs865686, 2df-<italic>P </italic>= 0.007; rs1292011 2df-<italic>P </italic>= 0.03. rs10771399 (<italic>PTHLH</italic>) was predominantly associated with estrogen receptor (ER)-negative breast cancer for <italic>BRCA1 </italic>mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, <italic>P</italic>-trend = 4 × 10<sup>-5</sup>) and there was marginal evidence of association with ER-negative breast cancer for <italic>BRCA2 </italic>mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, <italic>P</italic>-trend = 0.049).</p></sec><sec><title>Conclusions</title><p>The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers.</p></sec></abstract></article-meta></front><body><sec><title>Introduction</title><p>Pathogenic mutations in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>confer high risks of breast and ovarian cancers [<xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>]. Several lines of evidence suggest that these risks are modified by other genetic or environmental factors that cluster in families. Direct evidence for genetic modifiers of risk has been provided through studies that investigated the associations between common breast and ovarian cancer susceptibility variants, identified through genome-wide association studies (GWAS) or candidate gene studies in the general population, and cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers [<xref ref-type="bibr" rid="B3">3</xref>-<xref ref-type="bibr" rid="B8">8</xref>] and through GWAS in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers [<xref ref-type="bibr" rid="B9">9</xref>-<xref ref-type="bibr" rid="B11">11</xref>]. Six loci (at <italic>TOX3</italic>, 2q35, 6q25.1, 19p13, <italic>CASP8 </italic>and wild-type copy of <italic>BRCA1</italic>) are now known to be associated with breast cancer risk for <italic>BRCA1 </italic>mutation carriers; a further 10 loci (at <italic>FGFR2, TOX3, MAP3K1, LSP1</italic>, 2q35, <italic>SLC4A7</italic>, 5p12, 1p11.2, <italic>ZNF365 </italic>and <italic>RAD51</italic>) have been associated with breast cancer risk for <italic>BRCA2 </italic>carriers. The association patterns between these common variants and breast cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers are in general different, and mostly reflect differences in the associations of these single-nucleotide polymorphism (SNPs) with estrogen receptor (ER) status of breast cancer [<xref ref-type="bibr" rid="B12">12</xref>-<xref ref-type="bibr" rid="B14">14</xref>].</p><p>GWAS in the general population have recently identified eight additional breast cancer susceptibility loci which have not been previously investigated in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers. Turnbull <italic>et al. </italic>[<xref ref-type="bibr" rid="B15">15</xref>] identified five susceptibility loci on chromosomes 9 (rs1011970), 10 (rs2380205, rs10995190, rs704010) and 11 (rs614367) through a GWAS of breast cancer cases with a family history of the disease and unrelated controls. In a further follow-up of additional promising associations from that GWAS, the Breast Cancer Association Consortium (BCAC) has identified two additional loci at 12p11 (rs10771399) and 12q24 (rs1292011) which were associated with breast cancer risk in the general population [<xref ref-type="bibr" rid="B16">16</xref>]. The estimated odds ratios (OR) for ER-positive breast cancer for four of these SNPs (rs1011970 near <italic>CDKN2A/CDKN2B </italic>at chromosome 9, rs10995190 in <italic>ZNF365 </italic>at chromosome 10, rs614367 at 11q13 and rs1292011 at 12q24) were higher than the OR estimates for ER-negative breast cancer. In contrast, the OR estimates were similar for ER-positive and ER-negative breast cancer for SNPs rs2380205 (near <italic>ANKRD16 </italic>and <italic>FBXO18</italic>), rs704010 (upstream of <italic>ZMIZ1</italic>) and rs10771399 near <italic>PTHLH</italic>. In a separate GWAS that included mainly cases with two primary breast cancers or a family history of the disease, SNP rs865686 at 9q31.2 was found to be associated with risk for breast cancer, OR = 0.89 (95% CI: 0.85 to 0.92), but no estimates by ER status were reported [<xref ref-type="bibr" rid="B17">17</xref>].</p><p>The associations of these eight loci with breast cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers are still unknown. To evaluate these associations, we genotyped the eight SNPs in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers participating in the Consortium of Investigators of Modifiers of <italic>BRCA1/2 </italic>(CIMBA). We further investigated the associations with the risks of developing ER-positive and ER-negative breast cancer and the risk of ovarian cancer.</p></sec><sec sec-type="materials|methods"><title>Materials and methods</title><sec><title>Subjects</title><p>All carriers participated in clinical or research studies at the host institutions which have been approved by local ethics committees (list provided in Additional file <xref ref-type="supplementary-material" rid="S1">1</xref> Table S1). Informed consent was obtained from all study participants. Subjects were <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers recruited by 40 study centres in 28 countries through CIMBA (Additional file <xref ref-type="supplementary-material" rid="S1">1</xref> Table 2). The majority of carriers (97.58%) were recruited through cancer genetics clinics offering genetic testing, and enrolled into national or regional studies. Some carriers were identified by population-based sampling of cases (2.38%), and some by community recruitment (0.04%). Eligibility to participate in CIMBA is restricted to female carriers of pathogenic <italic>BRCA1 </italic>or <italic>BRCA2 </italic>mutations age 18 years old or older at recruitment. Information collected included the year of birth; mutation description, including nucleotide position and base change; self reported ethnic ancestry, age at last follow-up; ages at breast or ovarian cancer diagnoses; and age or date at bilateral prophylactic mastectomy and oophorectomy. Related individuals were identified through a unique family identifier. Women were included in the analysis if they carried mutations that were pathogenic according to generally recognized criteria [<xref ref-type="bibr" rid="B18">18</xref>]. Further details on CIMBA can be found elsewhere [<xref ref-type="bibr" rid="B19">19</xref>].</p><p>Women who carried pathogenic mutations in both <italic>BRCA1 </italic>and <italic>BRCA2 </italic>were excluded from the current analysis. The primary analysis was restricted to women self-reported as "white of European ancestry". The number of mutation carriers of non-white ancestry was too small to allow separate analysis. We investigated possible overlap of carriers between studies by comparing the year of birth, exact mutation description and the reported ages, to identify potential duplicate individuals. Where possible we also used other genotype data on SNPs genotyped in the current round (at least 26 SNPs), in previous genotyping rounds or as part of GWAS to find hidden duplicates. When a potential duplicate was identified, we contacted the relevant centres for further information about these individuals, in a manner that protected the identity of the individuals in question, in order to determine precisely the extent of true overlap in subjects and families appearing more than once in the data set. Duplicate mutation carriers were included only once in the analysis. When in doubt, and when centres could not clarify a potential duplication, one of the samples was excluded from the analysis.</p></sec><sec><title>Genotyping</title><p>DNA samples (in almost all cases, obtained from blood) were genotyped using the iPLEX Mass Array platform at four genotyping centres (Additional file <xref ref-type="supplementary-material" rid="S1">1</xref> Table S2); the iPLEX included 26 SNPs as part of a larger study. All centres included at least 2% of the samples in duplicate, no template controls in every plate, and a random mixture of affected and unaffected carriers. Samples that failed for ≥ 20% of all the SNPs typed (that is, five or more) were excluded from the analysis. A study was included in the analysis only if the call rate was over 95%, after samples that failed at multiple SNPs had been excluded. For each study, genotypes for at least 98% of the duplicate samples had to be concordant. To assess the accuracy of genotyping across genotyping centres, the four centres genotyped 95 DNA samples from a standard test plate (Coriell Institute) for all SNPs. If the genotyping was inconsistent for more than one sample in the test plate, all the studies genotyped at the centre were excluded from the analysis of that SNP. No SNPs failed this criterion. The present study included eight SNPs: rs1011970 (9p21, near <italic>CDKN2A/B</italic>), rs10995190 (10q21, near <italic>ZNF365</italic>), rs704010 (10q22, near ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near <italic>PTHLH</italic>) and rs865686 (9q31.2). Based on the quality control criteria, 4 studies were excluded from the analysis of rs2380205 (one due to low duplicate concordance, 3 due to low call rate), 2 studies were excluded from the analysis of rs704010 (low call rate) and 13 studies were excluded from the analysis of rs1292011 (all due to low call rates). As an additional genotyping quality-control check, we also evaluated the deviation from Hardy-Weinberg equilibrium (HWE) for unrelated subjects separately for each SNP and study. Nine studies had HWE <italic>P</italic>-values in the range 0.005 to 0.05 (two studies for rs10995190, two studies for rs704010, one study for rs10771399, two for rs1292011 and two for rs865686). Upon examination of the cluster plots for these studies and SNPs, none revealed any unusual patterns and these studies were included in all the analyses. After the above exclusions, a total of 19,731 unique mutation carriers (12,599 <italic>BRCA1 </italic>and 7,132 <italic>BRCA2</italic>) from 40 studies had an observed genotype for at least 1 of the SNPs and were included in the primary analysis.</p></sec><sec><title>Statistical analysis</title><p>The aim of the primary analysis was to evaluate the association between each genotype and breast cancer risk within a survival analysis framework. The time variable for each individual was defined to be the time to breast cancer diagnosis. Each individual was followed until the first breast cancer diagnosis, ovarian cancer diagnosis, or bilateral prophylactic mastectomy or the age at last observation. Only those with a first breast cancer diagnosis were considered as affected in the analysis. Mutation carriers censored at ovarian cancer diagnosis were considered unaffected. Analysis was conducted by modelling the retrospective likelihood of the observed genotypes conditional on the disease phenotypes as previously described [<xref ref-type="bibr" rid="B18">18</xref>]. The effect of each SNP was modelled either as a per-allele hazard ratio (HR) (multiplicative model) or as separate HRs for heterozygotes and homozygotes, and these were estimated on the logarithmic scale. The HRs were assumed to be independent of age (that is, we used a Cox proportional-hazards model). The assumption of proportional hazards was tested by adding a "genotype x age" interaction term to the model in order to fit models in which the HR changed with age. Analyses were carried out with the pedigree-analysis software MENDEL [<xref ref-type="bibr" rid="B20">20</xref>]; details of this approach have been described previously [<xref ref-type="bibr" rid="B18">18</xref>,<xref ref-type="bibr" rid="B21">21</xref>]. We examined between-study heterogeneity by comparing the models that allowed for study-specific log-hazard ratios against models in which the same log-hazard ratio was assumed to apply to all studies.</p><p>To investigate whether our results were influenced by any of our assumptions we performed additional sensitivity analyses. If a SNP is associated with disease survival, the inclusion of prevalent cases may influence the HR estimates. Current data indicate that five-year survival after a breast cancer diagnosis is over 80% (Cancer Research - UK, Breast cancer survival statistics) and studies have suggested no difference in survival between mutation carriers and non-carriers [<xref ref-type="bibr" rid="B22">22</xref>]. We, therefore, repeated our analysis by excluding mutation carriers diagnosed more than five years prior to recruitment into the study. To examine whether SNP associations differed by type of mutation, we classified <italic>BRCA1 </italic>mutations according to their potential functional effect [<xref ref-type="bibr" rid="B23">23</xref>-<xref ref-type="bibr" rid="B26">26</xref>]. Class 1 mutations were those likely to lead to the absence of protein expression due to i) reduced transcript level and/or degradation or instability of truncated proteins, or ii) absence of transcription. Class 1 mutations comprise truncating mutations expected to trigger nonsense-mediated mRNA decay (NMD) or translation re-initiation but no production of stable protein, and deletion of transcription regulatory regions. Class 2 mutations were those likely to generate stable mutant proteins with partial or total loss of function that might also have dominant negative effect. Class 2 mutations include missense substitutions, in-frame deletions and insertions, as well as truncating mutations with premature stop codons occurring in the last exon. Mutations whose consequences at transcript or protein level could not be inferred were not considered for this classification. These were mainly mutations located in splice sites but not characterised for their effect at the transcript level, or large deletions or insertions with undetermined boundaries.</p><p>The associations of these SNPs with ovarian cancer risk were evaluated within a competing risk analysis framework [<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B21">21</xref>], by estimating HRs simultaneously for breast and ovarian cancers. In this model, each individual was at risk of developing either breast or ovarian cancer, by assuming that the probabilities of developing each disease were independent conditional on the underlying genotype. A different censoring process was used for the competing risk analysis, whereby individuals were followed up to the age of the first breast or ovarian cancer diagnosis and were considered to have developed the corresponding disease. No follow-up was considered after the first cancer diagnosis. Individuals were censored for breast cancer at the age of bilateral prophylactic mastectomy and for ovarian cancer at the age of bilateral oophorectomy and were assumed to be unaffected for the corresponding disease. The remaining individuals were censored at the age at last observation and were assumed to be unaffected for both diseases.</p><p>We further evaluated the associations of these SNPs with breast cancer subtypes defined by the estrogen receptor (ER) status of the tumours in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers. The analysis was carried out by an extension of the retrospective likelihood approach to model the simultaneous effect of each SNP on more than one tumour subtype [<xref ref-type="bibr" rid="B14">14</xref>]. Briefly, this involves modelling the conditional likelihood of the observed SNP genotypes and tumour subtypes, given the disease phenotypes. Within this framework it is possible to estimate simultaneously the HRs for each tumour subtype and test for heterogeneity in the associations. Only studies that provided tumour pathology information and had genotype information were included in the analysis. To maximise the available information, genotyped mutation carriers that were missing information on tumour characteristics (within each study) were included in the analysis, and their disease subtype was assumed to be missing at random [<xref ref-type="bibr" rid="B14">14</xref>]. This is a reasonable assumption given that more than 90% of mutation carriers in our sample were recruited prior to 2007, when it was uncommon to use tumour pathology in selecting individuals for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation screening.</p><p>To ensure a sufficiently large number of mutation carriers within each stratum, we grouped studies from the same country. All analyses were stratified by country of residence and used calendar-year- and cohort-specific cancer incidences for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>[<xref ref-type="bibr" rid="B27">27</xref>]. For sensitivity analyses, strata with small numbers of mutation carriers were grouped. We used a robust variance-estimation approach to allow for the non-independence among related carriers [<xref ref-type="bibr" rid="B28">28</xref>].</p></sec></sec><sec sec-type="results"><title>Results</title><p>The analysis included 12,599 <italic>BRCA1 </italic>and 7,132 <italic>BRCA2 </italic>mutation carriers who were genotyped successfully for at least one of the eight SNPs. Table <xref ref-type="table" rid="T1">1</xref> summarises the characteristics of the mutation carriers used in the analysis. In evaluating associations with breast cancer, 10,200 mutation carriers had been diagnosed with a first breast cancer diagnosis, 1,869 were censored at an ovarian cancer diagnosis, 561 at age of bilateral prophylactic mastectomy and 7,101 at the age at last observation.</p><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Summary characteristics for the 19731 eligible <italic>BRCA1 </italic>and <italic>BRCA2 </italic>carriers* used in the analysis</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Characteristic</th><th align="center" colspan="2"><italic>BRCA1</italic></th><th align="center" colspan="2"><italic>BRCA2</italic></th></tr><tr><th></th><th align="center">Unaffected</th><th align="center">Breast cancer</th><th align="center">Unaffected</th><th align="center">Breast cancer</th></tr></thead><tbody><tr><td align="left">Number</td><td align="center">6,209</td><td align="center">6,390</td><td align="center">3,322</td><td align="center">3,810</td></tr><tr><td align="left">Person-years follow-up</td><td align="center">264,903</td><td align="center">263,068</td><td align="center">147,053</td><td align="center">168,201</td></tr><tr><td align="left">Median age at censure (IQR<sup>1</sup>)</td><td align="center">42 (34 to 50)</td><td align="center">40 (34 to 47)</td><td align="center">43 (34 to 53)</td><td align="center">43 (37 to 50)</td></tr><tr><td align="left">Age at censure, N (%)</td><td></td><td></td><td></td><td></td></tr><tr><td align="left">< 30</td><td align="center">1,189 (19.2)</td><td align="center">691 (10.8)</td><td align="center">611 (18.4)</td><td align="center">306 (8.0)</td></tr><tr><td align="left">30 to 39</td><td align="center">1,161 (26.8)</td><td align="center">2,445 (38.3)</td><td align="center">834 (25.1)</td><td align="center">1,141 (30.0)</td></tr><tr><td align="left">40 to 49</td><td align="center">1,765 (28.4)</td><td align="center">2,191 (34.3)</td><td align="center">865 (26.0)</td><td align="center">1,394 (36.6)</td></tr><tr><td align="left">50 to 59</td><td align="center">1,058 (17.0)</td><td align="center">812 (12.7)</td><td align="center">566 (17.0)</td><td align="center">687 (18.0)</td></tr><tr><td align="left">60 to 69</td><td align="center">380 (6.1)</td><td align="center">198 (3.1)</td><td align="center">302 (9.1)</td><td align="center">226 (5.9)</td></tr><tr><td align="left">70+</td><td align="center">156 (2.5)</td><td align="center">53 (0.8)</td><td align="center">144 (4.3)</td><td align="center">56 (1.5)</td></tr><tr><td align="left">Year of birth, N (%)</td><td></td><td></td><td></td><td></td></tr><tr><td align="left">< 1920</td><td align="center">28 (0.5)</td><td align="center">30 (0.5)</td><td align="center">23 (0.7)</td><td align="center">44 (1.2)</td></tr><tr><td align="left">1920 to 1929</td><td align="center">131 (2.1)</td><td align="center">196 (3.1)</td><td align="center">99 (3.0)</td><td align="center">167 (4.4)</td></tr><tr><td align="left">1930 to 1939</td><td align="center">369 (5.9)</td><td align="center">516 (8.1)</td><td align="center">232 (7.0)</td><td align="center">430 (11.3)</td></tr><tr><td align="left">1940 to 1949</td><td align="center">832 (13.4)</td><td align="center">1,341 (21.0)</td><td align="center">458 (13.8)</td><td align="center">896 (23.5)</td></tr><tr><td align="left">1950 to 1959</td><td align="center">1,409 (22.7)</td><td align="center">1,989 (31.1)</td><td align="center">691 (20.8)</td><td align="center">1,160 (30.5)</td></tr><tr><td align="left">1960 to 1969</td><td align="center">1,703 (27.4)</td><td align="center">1,666 (26.1)</td><td align="center">902 (27.2)</td><td align="center">868 (22.8)</td></tr><tr><td align="left">1970+</td><td align="center">1,737 (28.0)</td><td align="center">652 (10.2)</td><td align="center">917 (27.6)</td><td align="center">245 (6.4)</td></tr><tr><td align="left">Mutation Class, N (%)</td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class 1<sup>2</sup></td><td align="center">4,063 (65.4)</td><td align="center">3,878 (60.7)</td><td align="center">3,114 (93.7)</td><td align="center">3,520 (92.4)</td></tr><tr><td align="left">Class 2<sup>2</sup></td><td align="center">1,780 (28.7)</td><td align="center">1,973 (30.9)</td><td align="center">72 (2.2)</td><td align="center">100 (2.6)</td></tr><tr><td align="left">Other</td><td align="center">366 (5.9)</td><td align="center">539 (8.4)</td><td align="center">136 (4.1)</td><td align="center">190 (5.0)</td></tr></tbody></table><table-wrap-foot><p><sup>1 </sup>IQR: Interquartile Range</p><p><sup>2 </sup>See methods for definitions</p><p><italic>* </italic>Carriers of self-reported white European ancestry only.</p></table-wrap-foot></table-wrap><sec><title>Associations with cancer risk for BRCA1 mutation carriers</title><p>Of the eight SNPs, only rs10771399 in <italic>PTHLH </italic>was associated with breast cancer risk for <italic>BRCA1 </italic>mutation carriers (<italic>P</italic>-trend = 3 × 10<sup>-4</sup>, Table <xref ref-type="table" rid="T2">2</xref>). The association was consistent with a multiplicative model in which each copy of the minor allele was estimated to confer a HR of 0.87 (95% CI: 0.81 to 0.94). There was no evidence of heterogeneity in the HR estimates across studies (<italic>P</italic>-het = 0.24, Additional file <xref ref-type="supplementary-material" rid="S1">1</xref> Supplementary Figure 1). There was no evidence that the HRs varied with age (<italic>P </italic>= 0.68). The association remained significant, with a similar HR estimate (HR = 0.85, 95% CI: 0.77 to 0.93, <italic>P</italic>-trend = 6 × 10<sup>-4</sup>, Table <xref ref-type="table" rid="T3">3</xref>), when long-term survivors were excluded from the analysis, suggesting no evidence of survival bias. Interestingly, the association was restricted to <italic>BRCA1 </italic>carriers of Class 1 mutations (HR = 0.82, 95% CI: 0.74 to 0.90, <italic>P</italic>-trend = 3 × 10<sup>-5</sup>, Table <xref ref-type="table" rid="T3">3</xref>) with no evidence of association for Class 2 mutation carriers (HR = 1.00, 0.87 to 1.15, <italic>P</italic>-trend = 0.99, <italic>P</italic>-difference between Class 1 and Class 2 = 0.03).</p><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>SNP genotype distributions and associations with breast cancer risk.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Mutation</th><th align="left">Genotype</th><th align="center">Unaffected<break></break>N (%)</th><th align="center">Affected<sup>a</sup><break></break>N (%)</th><th align="center">HR</th><th align="center">95% CI</th><th align="center"><italic>P</italic>-value</th></tr></thead><tbody><tr><td align="left" colspan="2"><bold>CDK2NA/B - rs1011970</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">GG</td><td align="center">4,318 (69.7)</td><td align="center">4,460 (70.0)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GT</td><td align="center">1,698 (27.4)</td><td align="center">1,719 (27.0)</td><td align="center">1.01</td><td align="center">0.94 to 1.09</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">180 (2.9)</td><td align="center">195 (3.1)</td><td align="center">1.11</td><td align="center">0.91 to 1.35</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.61</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.03</td><td align="center">0.96 to 1.09</td><td align="center">0.45</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">GG</td><td align="center">2,279 (68.7)</td><td align="center">2,586 (67.9)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GT</td><td align="center">943 (28.4)</td><td align="center">1,098 (28.9)</td><td align="center">1.08</td><td align="center">0.98 to 1.19</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">94 (2.8)</td><td align="center">123 (3.2)</td><td align="center">1.23</td><td align="center">0.95 to 1.59</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.12</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center"><bold>1.09</bold></td><td align="center"><bold>1.00 to 1.18</bold></td><td align="center"><bold>0.048</bold></td></tr><tr><td align="left" colspan="3"><bold>ZNF365 - rs10995190</bold></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">GG</td><td align="center">4,394 (70.9)</td><td align="center">4,556 (71.5)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GA</td><td align="center">1,656 (26.7)</td><td align="center">1,662 (26.1)</td><td align="center">0.98</td><td align="center">0.91 to 1.06</td><td></td></tr><tr><td></td><td align="left">AA</td><td align="center">147 (2.4)</td><td align="center">156 (2.5)</td><td align="center">0.98</td><td align="center">0.79 to 1.20</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.89</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">0.99</td><td align="center">0.93 to 1.05</td><td align="center">0.64</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">GG</td><td align="center">2,334 (70.4)</td><td align="center">2,802 (73.7)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GA</td><td align="center">913 (27.5)</td><td align="center">923 (24.3)</td><td align="center"><bold>0.86</bold></td><td align="center"><bold>0.78 to 0.96</bold></td><td></td></tr><tr><td></td><td align="left">AA</td><td align="center">68 (20.1)</td><td align="center">79 (2.1)</td><td align="center">0.96</td><td align="center">0.69 to 1.34</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center"><bold>0.019</bold></td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center"><bold>0.90</bold></td><td align="center"><bold>0.82 to 0.98</bold></td><td align="center"><bold>0.015</bold></td></tr><tr><td align="left" colspan="3"><bold>ZMIZ1 - rs704010</bold></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">CC</td><td align="center">2,476 (40.3)</td><td align="center">2,504 (39.8)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">2,814 (45.8)</td><td align="center">2,894 (46.0)</td><td align="center">1.03</td><td align="center">0.96 to 1.10</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">855 (13.9)</td><td align="center">888 (14.1)</td><td align="center">1.04</td><td align="center">0.93 to 1.15</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.69</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.02</td><td align="center">0.97 to 1.07</td><td align="center">0.42</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">CC</td><td align="center">1,286 (39.3)</td><td align="center">1,443 (38.4)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,496 (45.7)</td><td align="center">1,779 (47.3)</td><td align="center">1.07</td><td align="center">0.97 to 1.18</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">494 (15.8)</td><td align="center">539 (14.3)</td><td align="center">0.99</td><td align="center">0.86 to 1.14</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.32</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.01</td><td align="center">0.95 to 1.08</td><td align="center">0.73</td></tr><tr><td align="left" colspan="2"><bold>10p15 - rs2380205</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">CC</td><td align="center">1,609 (32.5)</td><td align="center">1,710 (32.1)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">2,410 (48.7)</td><td align="center">2,625 (49.3)</td><td align="center">1.01</td><td align="center">0.93 to 1.09</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">933 (18.8)</td><td align="center">990 (18.6)</td><td align="center">1.02</td><td align="center">0.92 to 1.13</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.95</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.01</td><td align="center">0.96 to 1.06</td><td align="center">0.75</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">CC</td><td align="center">1,013 (32.8)</td><td align="center">1,163 (31.8)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,516 (49.1)</td><td align="center">1,816 (49.7)</td><td align="center">1.05</td><td align="center">0.95 to 1.16</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">560 (18.1)</td><td align="center">681 (18.6)</td><td align="center">1.03</td><td align="center">0.90 to 1.17</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.63</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.02</td><td align="center">0.96 to 1.09</td><td align="center">0.57</td></tr><tr><td align="left" colspan="3"><bold>11q13 - rs614367</bold></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">CC</td><td align="center">4,516 (73.2)</td><td align="center">4,581 (72.1)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,511 (24.5)</td><td align="center">1,618 (25.5)</td><td align="center">1.05</td><td align="center">0.98 to 1.14</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">146 (2.4)</td><td align="center">154 (2.4)</td><td align="center">1.07</td><td align="center">0.87 to 1.32</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.34</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.05</td><td align="center">0.98 to 1.12</td><td align="center">0.15</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">CC</td><td align="center">2,432 (73.6)</td><td align="center">2,723 (71.8)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">799 (24.1)</td><td align="center">983 (26.0)</td><td align="center">1.06</td><td align="center">0.96 to 1.17</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">76 (2.3)</td><td align="center">83 (2.2)</td><td align="center">0.97</td><td align="center">0.72 to 1.30</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.54</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.03</td><td align="center">0.95 to 1.12</td><td align="center">0.46</td></tr><tr><td align="left" colspan="3"><bold>12q24 - rs1292011</bold></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">AA</td><td align="center">1,292 (34.3)</td><td align="center">1,331 (35.4)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">1,825 (48.4)</td><td align="center">1,775 (47.3)</td><td align="center">0.98</td><td align="center">0.89 to 1.07</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">653 (17.3)</td><td align="center">649 (17.3)</td><td align="center">1.01</td><td align="center">0.90 to 1.14</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.80</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1.00</td><td align="center">0.94 to 1.06</td><td align="center">0.99</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">AA</td><td align="center">824 (35.2)</td><td align="center">908 (35.9)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">1,095 (46.7)</td><td align="center">1,225 (48.4)</td><td align="center">1.03</td><td align="center">0.92 to 1.16</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">423 (18.1)</td><td align="center">397 (15.7)</td><td align="center"><bold>0.84</bold></td><td align="center"><bold>0.72 to 0.99</bold></td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center"><bold>0.03</bold></td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">0.94</td><td align="center">0.87 to 1.01</td><td align="center">0.10</td></tr><tr><td align="left" colspan="2"><bold>PTHLH - rs10771399</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">AA</td><td align="center">4,913 (79.4)</td><td align="center">5,221 (82.0)</td><td align="center"><bold>1</bold></td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">1,194 (19.3)</td><td align="center">1,082 (17.0)</td><td align="center"><bold>0.87</bold></td><td align="center"><bold>0.80 to 0.95</bold></td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">83 (1.3)</td><td align="center">65 (1.0)</td><td align="center"><bold>0.77</bold></td><td align="center"><bold>0.57 to 1.04</bold></td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center"><bold>1.5 × 10<sup>-3</sup></bold></td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center"><bold>0.87</bold></td><td align="center"><bold>0.81 to 0.94</bold></td><td align="center"><bold>3.2 × 10<sup>-4</sup></bold></td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">AA</td><td align="center">2,649 (80.0)</td><td align="center">3,085 (81.2)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">620 (18.7)</td><td align="center">679 (17.9)</td><td align="center">0.95</td><td align="center">0.85 to 1.07</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">45 (1.4)</td><td align="center">34 (0.9)</td><td align="center">0.74</td><td align="center">0.47 to 1.15</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.31</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">0.93</td><td align="center">0.84 to 1.04</td><td align="center">0.20</td></tr><tr><td align="left" colspan="2"><bold>9q31.2 - rs865686</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">TT</td><td align="center">2,521 (40.1)</td><td align="center">2,640 (41.4)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">TG</td><td align="center">2,872 (46.4)</td><td align="center">2,849 (44.7)</td><td align="center">0.95</td><td align="center">0.88 to 1.01</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">799 (12.9)</td><td align="center">880 (13.8)</td><td align="center">1.05</td><td align="center">0.95 to 1.17</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center">0.06</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">1</td><td align="center">0.96 to 1.05</td><td align="center">0.85</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">TT</td><td align="center">1,277 (38.6)</td><td align="center">1,581 (41.6)</td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">TG</td><td align="center">1,610 (48.6)</td><td align="center">1,717 (45.2)</td><td align="center"><bold>0.86</bold></td><td align="center"><bold>0.78 to 0.95</bold></td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">425 (12.8)</td><td align="center">501 (13.2)</td><td align="center">0.96</td><td align="center">0.84 to 1.11</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td align="center"><bold>7.3 × 10<sup>-3</sup></bold></td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td align="center">0.95</td><td align="center">0.89 to 1.01</td><td align="center">0.10</td></tr></tbody></table><table-wrap-foot><p><sup>a </sup>Breast Cancer</p><p>HR, hazard ratio</p></table-wrap-foot></table-wrap><table-wrap id="T3" position="float"><label>Table 3</label><caption><p>Associations with breast cancer risk, after excluding prevalent breast cancer cases, and <italic>BRCA1 </italic>mutation class.</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th align="center">Unaffected, N</th><th align="center">Affected, N</th><th align="center">HR</th><th align="center">95% CI</th><th align="center"><italic>P</italic>-value</th></tr></thead><tbody><tr><td align="left" colspan="6"><bold>Excluding prevalent breast cancer cases</bold></td></tr><tr><td align="left"><bold>CDK2NA/B -rs1011970</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">6,200</td><td align="center">3,152</td><td align="center">1.05</td><td align="center">0.98 to 1.14</td><td align="center">0.18</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,319</td><td align="center">1,950</td><td align="center">1.10</td><td align="center">1.00 to 1.22</td><td align="center">0.05</td></tr><tr><td align="left"><bold>ZNF365 - rs10995190</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">6,201</td><td align="center">3,151</td><td align="center">0.96</td><td align="center">0.89 to 1.04</td><td align="center">0.34</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,318</td><td align="center">1,949</td><td align="center">0.90</td><td align="center">0.81 to 1.00</td><td align="center">0.05</td></tr><tr><td align="left"><bold>ZMIZ1 - rs704010</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">6,149</td><td align="center">3,094</td><td align="center">1.02</td><td align="center">0.96 to 1.08</td><td align="center">0.53</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,276</td><td align="center">1,919</td><td align="center">0.98</td><td align="center">0.91 to 1.06</td><td align="center">0.64</td></tr><tr><td align="left" colspan="5"><bold>10p15 - rs2380205</bold></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">4,955</td><td align="center">2,764</td><td align="center">1.02</td><td align="center">0.95 to 1.08</td><td align="center">0.64</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,092</td><td align="center">1,884</td><td align="center">1.00</td><td align="center">0.93 to 1.08</td><td align="center">0.92</td></tr><tr><td align="left"><bold>11q13 - rs614367</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">6,177</td><td align="center">3,144</td><td align="center">1.01</td><td align="center">0.94 to 1.10</td><td align="center">0.73</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,310</td><td align="center">1,944</td><td align="center">0.99</td><td align="center">0.89 to 1.10</td><td align="center">0.88</td></tr><tr><td align="left"><bold>12q24 - rs1292011</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">3,773</td><td align="center">1,798</td><td align="center">1.04</td><td align="center">0.97 to 1.12</td><td align="center">0.29</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">2,345</td><td align="center">1,220</td><td align="center">0.96</td><td align="center">0.88 to 1.06</td><td align="center">0.41</td></tr><tr><td align="left"><bold>PTHLH - rs10771399</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">6,194</td><td align="center">3,152</td><td align="center">0.85</td><td align="center">0.77 to 0.93</td><td align="center">5.8 × 10<sup>-4</sup></td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,317</td><td align="center">1,944</td><td align="center">0.89</td><td align="center">0.78 to 1.00</td><td align="center">0.06</td></tr><tr><td align="left"><bold>9q31.2 - rs865686</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="center">6,196</td><td align="center">3,149</td><td align="center">1.01</td><td align="center">0.95 to 1.07</td><td align="center">0.72</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="center">3,315</td><td align="center">1,946</td><td align="center">0.94</td><td align="center">0.87 to 1.02</td><td align="center">0.15</td></tr><tr><td align="left"><bold><italic>BRCA1 </italic>analysis by mutation class</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><bold>CDK2NA/B -rs1011970</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">4,040</td><td align="center">3,843</td><td align="center">1.01</td><td align="center">0.94 to 1.10</td><td align="center">0.72</td></tr><tr><td align="left">Class2</td><td align="center">1,771</td><td align="center">1,958</td><td align="center">1.03</td><td align="center">0.91 to 1.16</td><td align="center">0.66</td></tr><tr><td align="left"><bold>ZNF365 - rs10995190</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">4,058</td><td align="center">3,844</td><td align="center">.99</td><td align="center">0.92 to 1.07</td><td align="center">0.80</td></tr><tr><td align="left">Class2</td><td align="center">1,774</td><td align="center">1,957</td><td align="center">0.97</td><td align="center">0.86 to 1.09</td><td align="center">0.59</td></tr><tr><td align="left"><bold>ZMIZ1 - rs704010</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">3,998</td><td align="center">3,787</td><td align="center">1.04</td><td align="center">0.98 to 1.10</td><td align="center">0.22</td></tr><tr><td align="left">Class2</td><td align="center">1,767</td><td align="center">1,936</td><td align="center">1.01</td><td align="center">0.92 to 1.11</td><td align="center">0.85</td></tr><tr><td align="left" colspan="6"><bold>10p15 - rs2380205</bold></td></tr><tr><td align="left">Class1</td><td align="center">3,664</td><td align="center">3,538</td><td align="center">1.01</td><td align="center">0.95 to 1.07</td><td align="center">0.82</td></tr><tr><td align="left">Class2</td><td align="center">931</td><td align="center">1,263</td><td align="center">1.03</td><td align="center">0.91 to 1.15</td><td align="center">0.67</td></tr><tr><td align="left"><bold>11q13 - rs614367</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">4,024</td><td align="center">3,833</td><td align="center">1.10</td><td align="center">1.02 to 1.19</td><td align="center">0.02</td></tr><tr><td align="left">Class2</td><td align="center">1,764</td><td align="center">1,948</td><td align="center">0.94</td><td align="center">0.84 to 1.06</td><td align="center">0.32</td></tr><tr><td align="left"><bold>12q24 - rs1292011</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">2,812</td><td align="center">2,521</td><td align="center">0.99</td><td align="center">0.92 to 1.06</td><td align="center">0.71</td></tr><tr><td align="left">Class2</td><td align="center">642</td><td align="center">797</td><td align="center">0.97</td><td align="center">0.84 to 1.12</td><td align="center">0.68</td></tr><tr><td align="left"><bold>PTHLH - rs10771399</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">4,035</td><td align="center">3,841</td><td align="center">0.82</td><td align="center">0.74 to 0.90</td><td align="center">3.1 × 10<sup>-5</sup></td></tr><tr><td align="left">Class2</td><td align="center">1,770</td><td align="center">1,953</td><td align="center">1.00</td><td align="center">0.87 to 1.15</td><td align="center">0.99</td></tr><tr><td align="left"><bold>9q31.2 - rs865686</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Class1</td><td align="center">4,038</td><td align="center">3,840</td><td align="center">0.98</td><td align="center">0.92 to 1.04</td><td align="center">0.48</td></tr><tr><td align="left">Class2</td><td align="center">1,769</td><td align="center">1,957</td><td align="center">1.03</td><td align="center">0.94 to 1.14</td><td align="center">0.49</td></tr></tbody></table><table-wrap-foot><p>HR, hazard ratio</p></table-wrap-foot></table-wrap><p>We found no evidence of association between breast cancer risk for <italic>BRCA1 </italic>mutation carriers and any of the other SNPs under the trend models (<italic>P</italic>-trend > 0.15). There was, however, some suggestion of an association under the genotype specific model for rs865686 (2df <italic>P </italic>= 0.06, Table <xref ref-type="table" rid="T2">2</xref>), reflecting a lower HR for heterozygous carriers than for either homozygote genotype. There was marginal evidence of heterogeneity in the HRs across countries for rs704010 and rs865686 (<italic>P</italic>-het = 0.04 for both), but examination of the forest plots revealed that in each case this was mainly due to a single study/country of relatively small sample size, with the majority of the HR estimates being close to 1 (Additional file <xref ref-type="supplementary-material" rid="S1">1</xref> Supplementary Figure 1). There was no evidence that the HRs varied by age for any of the SNPs (<italic>P </italic>> 0.08 for all).</p><p>We further evaluated the SNP associations with breast and ovarian cancer risk simultaneously (Table <xref ref-type="table" rid="T4">4</xref>). The associations with breast cancer risk remained essentially unchanged in the competing risk analysis, with only the <italic>PTHLH </italic>SNP rs10771399 being significantly associated with breast cancer risk. There was some suggestion of a possible association between this SNP and ovarian cancer risk for <italic>BRCA1 </italic>mutation carriers with risk in the opposite direction (HR for ovarian cancer = 1.14, 95% CI: 1.00 to 1.30, <italic>P</italic>-trend = 0.06) especially among rare homozygotes (ovarian cancer HR for GG = 1.67, 95% CI: 1.05 to 2.64, <italic>P</italic>-homozygotes = 0.03). This analysis also provided some weak evidence for an association between SNP rs614367 at 11q13 and ovarian cancer risk for <italic>BRCA1 </italic>mutation carriers under the genotype-specific model (2df <italic>P</italic>-value = 0.03). There was no evidence that any of the other SNPs are associated with ovarian cancer risk for <italic>BRCA1 </italic>mutation carriers.</p><table-wrap id="T4" position="float"><label>Table 4</label><caption><p>Competing risk analysis*.</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th></th><th></th><th></th><th></th><th align="center" colspan="3">Breast cancer</th><th align="center" colspan="3">Ovarian cancer</th></tr><tr><th></th><th></th><th align="center">Unaffected<break></break>N (%)</th><th align="center">Breast<break></break>cancer<break></break>N (%)</th><th align="center">Ovarian<break></break>cancer<break></break>N (%)</th><th align="center">HR</th><th align="center">95% CI</th><th align="center"><italic>P</italic>-value</th><th align="center">HR</th><th align="center">95% CI</th><th align="center"><italic>P</italic>-value</th></tr></thead><tbody><tr><td align="left" colspan="2"><bold>CDK2NA/B - rs1011970</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">GG</td><td align="center">3,328 (69.6)</td><td align="center">4,424 (69.9)</td><td align="center">1,026 (70.1)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GT</td><td align="center">1,309 (27.4)</td><td align="center">1,710 (27.0)</td><td align="center">398 (27.2)</td><td align="center">1.03</td><td align="center">0.95 to 1.11</td><td></td><td align="center">1.10</td><td align="center">0.95 to 1.26</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">142 (3.0)</td><td align="center">194 (3.1)</td><td align="center">39 (2.7)</td><td align="center">1.09</td><td align="center">0.88 to 1.35</td><td></td><td align="center">0.90</td><td align="center">0.61 to 1.32</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.57</td><td></td><td></td><td align="center">0.35</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.04</td><td align="center">0.91 to 1.11</td><td align="center">0.30</td><td align="center">1.04</td><td align="center">0.93 to 1.17</td><td align="center">0.48</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">GG</td><td align="center">1,972 (68.6)</td><td align="center">2578 (67.9)</td><td align="center">315 (69.5)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GT</td><td align="center">815 (28.4)</td><td align="center">1097 (28.9)</td><td align="center">129 (28.5)</td><td align="center">1.09</td><td align="center">0.98 to 1.21</td><td></td><td align="center">1.07</td><td align="center">0.85 to 1.35</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">86 (3.0)</td><td align="center">122 (3.2)</td><td align="center">9 (2.0)</td><td align="center">1.19</td><td align="center">0.91 to 1.57</td><td></td><td align="center">0.84</td><td align="center">0.40 to 1.77</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.15</td><td></td><td></td><td align="center">0.74</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center"><bold>1.09</bold></td><td align="center"><bold>1.00 to 1.19</bold></td><td align="center"><bold>0.05</bold></td><td align="center">1.03</td><td align="center">0.84 to 1.25</td><td align="center">0.81</td></tr><tr><td align="left"><bold>ZNF365 - rs10995190</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">GG</td><td align="center">3,408 (71.3)</td><td align="center">4,523 (71.5)</td><td align="center">1,019 (69.6)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GA</td><td align="center">1,258 (26.3)</td><td align="center">1,650 (26.1)</td><td align="center">410 (28.0)</td><td align="center">1.00</td><td align="center">0.93 to 1.08</td><td></td><td align="center">1.12</td><td align="center">0.98 to 1.28</td><td></td></tr><tr><td></td><td align="left">AA</td><td align="center">113 (2.4)</td><td align="center">155 (2.5)</td><td align="center">35 (2.4)</td><td align="center">0.96</td><td align="center">0.78 to 1.20</td><td></td><td align="center">0.90</td><td align="center">0.61 to 1.33</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.94</td><td></td><td></td><td align="center">0.23</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">0.99</td><td align="center">0.93 to 1.06</td><td align="center">0.88</td><td align="center">1.06</td><td align="center">0.95 to 1.19</td><td align="center">0.32</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">GG</td><td align="center">2,033 (70.4)</td><td align="center">2,795 (73.7)</td><td align="center">318 (70.2)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">GA</td><td align="center">794 (27.7)</td><td align="center">920 (24.3)</td><td align="center">122 (26.9)</td><td align="center"><bold>0.86</bold></td><td align="center"><bold>0.78 to 0.96</bold></td><td></td><td align="center">0.99</td><td align="center">0.78 to 1.25</td><td></td></tr><tr><td></td><td align="left">AA</td><td align="center">55 (1.9)</td><td align="center">79 (2.1)</td><td align="center">13 (2.9)</td><td align="center">1.03</td><td align="center">0.74 to 1.43</td><td></td><td align="center">1.58</td><td align="center">0.83 to 3.03</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center"><bold>0.02</bold></td><td></td><td></td><td align="center">0.37</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center"><bold>0.90</bold></td><td align="center"><bold>0.82 to 0.99</bold></td><td align="center"><bold>0.03</bold></td><td align="center">1.06</td><td align="center">0.87 to 1.31</td><td align="center">0.55</td></tr><tr><td align="left"><bold>ZMIZ1 - rs704010</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">CC</td><td align="center">1,904 (40.2)</td><td align="center">2,493 (40.0)</td><td align="center">583 (40.1)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">2,172 (45.9)</td><td align="center">2,871 (46.0)</td><td align="center">665 (45.7)</td><td align="center">1.02</td><td align="center">0.95 to 1.10</td><td></td><td align="center">1.01</td><td align="center">0.89 to 1.15</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">660 (13.9)</td><td align="center">877 (14.1)</td><td align="center">206 (14.2)</td><td align="center">1.02</td><td align="center">0.92 to 1.14</td><td></td><td align="center">1.01</td><td align="center">0.84 to 1.22</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.67</td><td></td><td></td><td align="center">0.99</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.01</td><td align="center">0.97 to 1.07</td><td align="center">0.58</td><td align="center">1.01</td><td align="center">0.92 to 1.10</td><td align="center">0.90</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">CC</td><td align="center">1,109 (39.0)</td><td align="center">1,439 (38.4)</td><td align="center">181 (40.1)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,306 (46.0)</td><td align="center">1,774 (47.3)</td><td align="center">192 (43.4)</td><td align="center">1.06</td><td align="center">0.96 to 1.17</td><td></td><td align="center">0.96</td><td align="center">0.76 to 1.20</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">426 (15.0)</td><td align="center">538 (14.3)</td><td align="center">69 (15.6)</td><td align="center">1.00</td><td align="center">0.86 to 1.15</td><td></td><td align="center">1.05</td><td align="center">0.77 to 1.43</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.46</td><td></td><td></td><td align="center">0.81</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.01</td><td align="center">0.95 to 1.08</td><td align="center">0.72</td><td align="center">1.01</td><td align="center">0.87 to 1.18</td><td align="center">0.90</td></tr><tr><td align="left" colspan="3"><bold>10p15 - rs2380205</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">CC</td><td align="center">1,183 (32.2)</td><td align="center">1,698 (32.1)</td><td align="center">438 (33.2)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,796 (48.9)</td><td align="center">2,605 (49.3)</td><td align="center">634 (48.1)</td><td align="center">0.99</td><td align="center">0.91 to 1.08</td><td></td><td align="center">0.91</td><td align="center">0.79 to 1.05</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">696 (18.9)</td><td align="center">981 (18.6)</td><td align="center">246 (18.7)</td><td align="center">1.00</td><td align="center">0.90 to 1.12</td><td></td><td align="center">0.94</td><td align="center">0.78 to 1.14</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.96</td><td></td><td></td><td align="center">0.45</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.00</td><td align="center">0.95 to 1.06</td><td align="center">0.98</td><td align="center">0.96</td><td align="center">0.87 to 1.06</td><td align="center">0.40</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">CC</td><td align="center">872 (32.6)</td><td align="center">1,161 (31.8)</td><td align="center">143 (33.7)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,321 (49.4)</td><td align="center">1,812 (49.6)</td><td align="center">199 (46.9)</td><td align="center">1.04</td><td align="center">0.94 to 1.16</td><td></td><td align="center">0.94</td><td align="center">0.74 to 1.19</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">481 (18.0)</td><td align="center">678 (18.6)</td><td align="center">82 (19.3)</td><td align="center">1.03</td><td align="center">0.90 to 1.18</td><td></td><td align="center">1.01</td><td align="center">0.75 to 1.38</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.74</td><td></td><td></td><td align="center">0.82</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.02</td><td align="center">0.95 to 1.09</td><td align="center">0.61</td><td align="center">1.00</td><td align="center">0.85 to 1.16</td><td align="center">0.98</td></tr><tr><td align="left" colspan="3"><bold>11q13 - rs614367</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">CC</td><td align="center">3,439 (72.3)</td><td align="center">4,547 (72.1)</td><td align="center">1,111 (76.2)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">1,212 (25.5)</td><td align="center">1,606 (25.5)</td><td align="center">311 (21.3)</td><td align="center">1.02</td><td align="center">0.94 to 1.11</td><td></td><td align="center"><bold>0.83</bold></td><td align="center"><bold>0.72 to 0.96</bold></td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">109 (2.3)</td><td align="center">154 (2.4)</td><td align="center">37 (2.5)</td><td align="center">1.12</td><td align="center">0.91 to 1.39</td><td></td><td align="center">1.20</td><td align="center">0.81 to 1.76</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.52</td><td></td><td></td><td align="center"><bold>0.03</bold></td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.03</td><td align="center">0.91 to 1.10</td><td align="center">0.35</td><td align="center">0.91</td><td align="center">0.80 to 1.03</td><td align="center">0.13</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">CC</td><td align="center">2,106 (73.5)</td><td align="center">2,716 (71.9)</td><td align="center">333 (73.8)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">CT</td><td align="center">693 (24.2)</td><td align="center">981 (26.0)</td><td align="center">108 (24.0)</td><td align="center">1.05</td><td align="center">0.95 to 1.16</td><td></td><td align="center">0.95</td><td align="center">0.74 to 1.21</td><td></td></tr><tr><td></td><td align="left">TT</td><td align="center">66 (2.3)</td><td align="center">83 (2.2)</td><td align="center">10 (2.2)</td><td align="center">0.96</td><td align="center">0.71 to 1.28</td><td></td><td align="center">0.87</td><td align="center">0.46 to 1.63</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.62</td><td></td><td></td><td align="center">0.84</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.03</td><td align="center">0.94 to 1.12</td><td align="center">0.56</td><td align="center">0.94</td><td align="center">0.77 to 1.15</td><td align="center">0.56</td></tr><tr><td align="left" colspan="3"><bold>12q24 - rs1292011</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">AA</td><td align="center">997 (34.1)</td><td align="center">1,321 (35.4)</td><td align="center">305 (34.9)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">1,406 (48.2)</td><td align="center">1,765 (47.3)</td><td align="center">429 (49.1)</td><td align="center">1.00</td><td align="center">0.90 to 1.10</td><td></td><td align="center">1.11</td><td align="center">0.93 to 1.31</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">517 (17.7)</td><td align="center">645 (17.3)</td><td align="center">140 (16.0)</td><td align="center">1.01</td><td align="center">0.89 to 1.15</td><td></td><td align="center">0.98</td><td align="center">0.78 to 1.24</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.97</td><td></td><td></td><td align="center">0.39</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.00</td><td align="center">0.94 to 1.07</td><td align="center">0.91</td><td align="center">1.01</td><td align="center">0.91 to 1.13</td><td align="center">0.82</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">AA</td><td align="center">715 (35.0)</td><td align="center">907 (35.9)</td><td align="center">110 (36.5)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">961 (47.0)</td><td align="center">1222 (48.4)</td><td align="center">137 (45.5)</td><td align="center">1.02</td><td align="center">0.90 to 1.15</td><td></td><td align="center">0.94</td><td align="center">0.71 to 1.25</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">370 (18.1)</td><td align="center">396 (15.7)</td><td align="center">54 (17.9)</td><td align="center"><bold>0.83</bold></td><td align="center"><bold>0.70 to 0.97</bold></td><td></td><td align="center">0.89</td><td align="center">0.61 to 1.28</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center"><bold>0.03</bold></td><td></td><td></td><td align="center">0.80</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">0.93</td><td align="center">0.86 to 1.00</td><td align="center">0.07</td><td align="center">0.94</td><td align="center">0.78 to 1.13</td><td align="center">0.51</td></tr><tr><td align="left" colspan="3"><bold>PTHLH - rs10771399</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">AA</td><td align="center">3,810 (79.8)</td><td align="center">5,179 (81.9)</td><td align="center">1,145 (78.4)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">909 (19.0)</td><td align="center">1078 (17.1)</td><td align="center">289 (19.8)</td><td align="center">0.89</td><td align="center">0.81 to 0.97</td><td></td><td align="center">1.09</td><td align="center">0.93 to 1.26</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">56 (1.2)</td><td align="center">65 (1.0)</td><td align="center">27 (1.9)</td><td align="center"><bold>0.86</bold></td><td align="center"><bold>0.63 to 1.16</bold></td><td></td><td align="center"><bold>1.67</bold></td><td align="center"><bold>1.05 to 2.64</bold></td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center"><bold>0.02</bold></td><td></td><td></td><td align="center">0.06</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center"><bold>0.90</bold></td><td align="center"><bold>0.83 to 0.97</bold></td><td align="center"><bold>6.4 × 10<sup>-3</sup></bold></td><td align="center">1.14</td><td align="center">1.00 to 1.30</td><td align="center">0.06</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">AA</td><td align="center">2,289 (79.7)</td><td align="center">3,076 (81.2)</td><td align="center">369 (81.5)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">AG</td><td align="center">545 (19.0)</td><td align="center">678 (17.9)</td><td align="center">76 (16.8)</td><td align="center">0.94</td><td align="center">0.84 to 1.06</td><td></td><td align="center">0.88</td><td align="center">0.67 to 1.16</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">37 (1.3)</td><td align="center">34 (0.9)</td><td align="center">8 (1.8)</td><td align="center">0.79</td><td align="center">0.49 to 1.26</td><td></td><td align="center">1.48</td><td align="center">0.63 to 3.46</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.38</td><td></td><td></td><td align="center">0.43</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">0.93</td><td align="center">0.84 to 1.04</td><td align="center">0.19</td><td align="center">0.96</td><td align="center">0.75 to 1.23</td><td align="center">0.75</td></tr><tr><td align="left" colspan="3"><bold>9q31.2 - rs865686</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">TT</td><td align="center">1,935 (40.5)</td><td align="center">2,621 (41.5)</td><td align="center">605 (41.3)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">TG</td><td align="center">2,206 (46.2)</td><td align="center">2,825 (44.7)</td><td align="center">690 (47.1)</td><td align="center">0.94</td><td align="center">0.88 to 1.01</td><td></td><td align="center">0.99</td><td align="center">0.87 to 1.12</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">633 (13.3)</td><td align="center">877 (13.9)</td><td align="center">169 (11.5)</td><td align="center">1.03</td><td align="center">0.93 to 1.15</td><td></td><td align="center">0.85</td><td align="center">0.70 to 1.03</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center">0.12</td><td></td><td></td><td align="center">0.23</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">1.00</td><td align="center">0.95 to 1.05</td><td align="center">0.88</td><td align="center">0.94</td><td align="center">0.86 to 1.03</td><td align="center">0.17</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">TT</td><td align="center">1,103 (38.4)</td><td align="center">1,576 (41.6)</td><td align="center">179 (39.6)</td><td align="center">1</td><td></td><td></td><td align="center">1</td><td></td><td></td></tr><tr><td></td><td align="left">TG</td><td align="center">1400 (48.8)</td><td align="center">1712 (45.2)</td><td align="center">215 (47.6)</td><td align="center"><bold>0.85</bold></td><td align="center"><bold>0.77 to 0.94</bold></td><td></td><td align="center">0.91</td><td align="center">0.73 to 1.14</td><td></td></tr><tr><td></td><td align="left">GG</td><td align="center">367 (12.8)</td><td align="center">501 (13.2)</td><td align="center">58 (12.8)</td><td align="center">0.97</td><td align="center">0.84 to 1.12</td><td></td><td align="center">0.98</td><td align="center">0.71 to 1.35</td><td></td></tr><tr><td></td><td align="left">2-df test</td><td></td><td></td><td></td><td></td><td></td><td align="center"><bold>4.6 × 10<sup>-3</sup></bold></td><td></td><td></td><td align="center">0.70</td></tr><tr><td></td><td align="left">per allele</td><td></td><td></td><td></td><td align="center">0.94</td><td align="center">0.88 to 1.01</td><td align="center">0.10</td><td align="center">0.97</td><td align="center">0.83 to 1.13</td><td align="center">0.67</td></tr></tbody></table><table-wrap-foot><p>Associations with breast and ovarian cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>carriers.</p><p>*Censoring process described in the methods</p><p>HR, hazard ratio</p></table-wrap-foot></table-wrap></sec><sec><title>Associations with cancer risk for BRCA2 mutation carriers</title><p>There was evidence of association with breast cancer risk for <italic>BRCA2 </italic>mutation carriers for four SNPs (Table <xref ref-type="table" rid="T2">2</xref>). The minor allele of rs10995190 in <italic>ZNF365 </italic>was associated with a reduced risk of breast cancer, where each copy of allele "A" was estimated to confer a HR of 0.90 (95% CI: 0.82 to 0.98, <italic>P</italic>-trend = 0.015). There was also some marginal evidence that the minor allele of rs1011970 near <italic>CDKN2A/CDKN2B </italic>was associated with increased breast cancer risk (HR = 1.09, 95% CI: 1.00 to 1.18, <italic>P</italic>-trend = 0.048). None of the other polymorphisms was associated with breast cancer risk for <italic>BRCA2 </italic>mutation carriers under the multiplicative model. However, SNPs rs865686 and rs1292011 were associated with risk under the genotype specific model (2df-<italic>P </italic>= 0.007 and 0.03 respectively, Table <xref ref-type="table" rid="T2">2</xref>). There was some evidence of heterogeneity in the HRs across countries for rs1011970 (<italic>P</italic>-het = 0.005). This appeared to be mainly due to the USA stratum. The heterogeneity was no longer significant after removal of that stratum (<italic>P</italic>-het = 0.42) and the HR estimate for the association with breast cancer risk increased to 1.20 (95% CI: 1.09 to 1.32, <italic>P</italic>-trend = 1 × 10<sup>-4</sup>). There was no heterogeneity for any of the other SNPs (<italic>P</italic>-het > 0.12 for all, Additional file <xref ref-type="supplementary-material" rid="S1">1</xref> Supplementary Figure 2). The HR estimates for the four associated SNPs were similar when long-term survivors were excluded from the analysis (Table <xref ref-type="table" rid="T3">3</xref>). Consistent with the results of the main analysis, rs10995190 in <italic>ZNF365 </italic>and rs1011970 near <italic>CDKN2A/CDKN2B </italic>provided marginal evidence of association using the trend-test statistic (<italic>P</italic>-trend = 0.05 for both) and SNPs rs865686 was associated with breast cancer risk under the genotype specific model (2df-<italic>P </italic>= 0.03). SNP rs1292011 was not associated with breast cancer risk in this analysis. A somewhat smaller HR estimate was obtained for the <italic>PTHLH </italic>SNP rs10771399 compared to the main analysis (per-allele HR = 0.89, 95% CI: 0.78 to 1.00, <italic>P</italic>-trend = 0.06). The attenuation of the association in the overall analysis could have occurred if the SNP is also associated with prognosis. However, the difference in the HRs was small. The results for the remaining SNPs were similar and non-significant. None of SNPs were associated with ovarian cancer risk for <italic>BRCA2 </italic>mutation carriers (Table <xref ref-type="table" rid="T4">4</xref>).</p></sec><sec><title>Associations by tumour ER-status</title><p>Table <xref ref-type="table" rid="T5">5</xref> summarises the associations of the eight SNPs with breast cancer ER status in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers. Only the <italic>PTHLH </italic>SNP rs10771399 was associated with ER-negative breast cancer for <italic>BRCA1 </italic>mutation carriers (ER-negative HR = 0.81, 95% CI: 0.74 to 0.90, <italic>P</italic>-trend = 3.8 × 10<sup>-5</sup>). There was also marginal evidence that SNP rs704010 near <italic>ZMIZ1 </italic>was associated with ER-positive breast cancer for <italic>BRCA1 </italic>mutation carriers (ER-positive HR = 1.12, 95% CI: 1.00 to 1.26, <italic>P</italic>-trend = 0.046). However, the associations between ER-negative and ER-positive breast cancer among <italic>BRCA1 </italic>mutation carriers were only significantly different for SNP rs1292011 at 12q24 (<italic>P</italic>-heterogeneity = 0.045).</p><table-wrap id="T5" position="float"><label>Table 5</label><caption><p>Associations with estrogen receptor-positive and estrogen receptor-negative breast cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>carriers.</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th></th><th></th><th></th><th></th><th align="center" colspan="3">ER-positive</th><th align="center" colspan="3">ER-negative</th><th></th></tr><tr><th></th><th align="left">Unaffected<break></break>N</th><th align="center">ER-positive N</th><th align="center">ER-negative N</th><th align="center">ER status unknown N</th><th align="center">HR</th><th align="center">95% CI</th><th align="center"><italic>P</italic>-value</th><th align="center">HR</th><th align="center">95% CI</th><th align="center"><italic>P</italic>-value</th><th align="center">P-dif</th></tr></thead><tbody><tr><td align="left" colspan="2"><bold>CDK2NA/B - rs1011970</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,893</td><td align="center">559</td><td align="center">1,888</td><td align="center">2,841</td><td align="center">0.95</td><td align="center">0.81 to 1.12</td><td align="center">0.56</td><td align="center">1.03</td><td align="center">0.95 to 1.11</td><td align="center">0.47</td><td align="center">0.41</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,928</td><td align="center">1,372</td><td align="center">424</td><td align="center">1,649</td><td align="center"><bold>1.10</bold></td><td align="center"><bold>1.00 to 1.22</bold></td><td align="center"><bold>0.05</bold></td><td align="center">1.15</td><td align="center">0.96 to 1.37</td><td align="center">0.12</td><td align="center">0.70</td></tr><tr><td align="left" colspan="2"><bold>ZNF365 - rs10995190</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,895</td><td align="center">559</td><td align="center">1,887</td><td align="center">2,843</td><td align="center">0.88</td><td align="center">0.74 to 1.04</td><td align="center">0.14</td><td align="center">1.01</td><td align="center">0.94 to 1.10</td><td align="center">0.75</td><td align="center">0.16</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,927</td><td align="center">1,370</td><td align="center">406</td><td align="center">1,648</td><td align="center"><bold>0.89</bold></td><td align="center"><bold>0.80 to 1.00</bold></td><td align="center"><bold>0.043</bold></td><td align="center">0.87</td><td align="center">0.71 to 1.07</td><td align="center">0.19</td><td align="center">0.84</td></tr><tr><td align="left" colspan="2"><bold>ZMIZ1 - rs704010</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,842</td><td align="center">548</td><td align="center">1,846</td><td align="center">2,811</td><td align="center"><bold>1.12</bold></td><td align="center"><bold>1.00 to 1.26</bold></td><td align="center"><bold>0.046</bold></td><td align="center">1.00</td><td align="center">0.94 to 1.06</td><td align="center">0.91</td><td align="center">0.08</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,887</td><td align="center">1,347</td><td align="center">401</td><td align="center">1,636</td><td align="center">1.01</td><td align="center">0.93 to 1.09</td><td align="center">0.91</td><td align="center">1.00</td><td align="center">0.87 to 1.14</td><td align="center">0.95</td><td align="center">0.91</td></tr><tr><td align="left" colspan="2"><bold>10p15 - rs2380205</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,465</td><td align="center">540</td><td align="center">1,812</td><td align="center">2,513</td><td align="center">0.90</td><td align="center">0.80 to 1.01</td><td align="center">0.08</td><td align="center">1.02</td><td align="center">0.96 to 1.09</td><td align="center">0.46</td><td align="center">0.06</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,701</td><td align="center">1,341</td><td align="center">396</td><td align="center">1,543</td><td align="center">1.02</td><td align="center">0.95 to 1.10</td><td align="center">0.60</td><td align="center">0.94</td><td align="center">0.82 to 1.08</td><td align="center">0.39</td><td align="center">0.31</td></tr><tr><td align="left" colspan="2"><bold>11q13 - rs614367</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,879</td><td align="center">557</td><td align="center">1,886</td><td align="center">2,832</td><td align="center">1.09</td><td align="center">0.93 to 1.29</td><td align="center">0.30</td><td align="center">1.04</td><td align="center">0.96 to 1.12</td><td align="center">0.40</td><td align="center">0.59</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,921</td><td align="center">1,365</td><td align="center">405</td><td align="center">1,639</td><td align="center">1.06</td><td align="center">0.96 to 1.17</td><td align="center">0.26</td><td align="center">0.84</td><td align="center">0.69 to 1.04</td><td align="center">0.10</td><td align="center">0.05</td></tr><tr><td align="left" colspan="2"><bold>12q24 - rs1292011</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">3,429</td><td align="center">308</td><td align="center">1,043</td><td align="center">2,031</td><td align="center">0.87</td><td align="center">0.74 to 1.02</td><td align="center">0.09</td><td align="center">1.05</td><td align="center">0.98 to 1.13</td><td align="center">0.12</td><td align="center"><bold>0.046</bold></td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,065</td><td align="center">813</td><td align="center">239</td><td align="center">1,170</td><td align="center">0.95</td><td align="center">0.86 to 1.04</td><td align="center">0.28</td><td align="center">0.98</td><td align="center">0.82 to 1.16</td><td align="center">0.78</td><td align="center">0.79</td></tr><tr><td align="left" colspan="2"><bold>PTHLH - rs10771399</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,889</td><td align="center">557</td><td align="center">1,887</td><td align="center">2,842</td><td align="center">0.94</td><td align="center">0.78 to 1.13</td><td align="center">0.52</td><td align="center"><bold>0.81</bold></td><td align="center"><bold>0.74 to 0.90</bold></td><td align="center"><bold>3.8 × 10<sup>-5</sup></bold></td><td align="center">0.20</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,926</td><td align="center">1,366</td><td align="center">406</td><td align="center">1,648</td><td align="center">0.97</td><td align="center">0.86 to 1.10</td><td align="center">0.68</td><td align="center"><bold>0.78</bold></td><td align="center"><bold>0.62 to 1.00</bold></td><td align="center"><bold>0.049</bold></td><td align="center">0.12</td></tr><tr><td align="left" colspan="2"><bold>9q31.2 - rs865686</bold></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left"><italic>BRCA1</italic></td><td align="left">4,892</td><td align="center">559</td><td align="center">1,888</td><td align="center">2,836</td><td align="center">0.92</td><td align="center">0.81 to 1.03</td><td align="center">0.15</td><td align="center">1.01</td><td align="center">0.95 to 1.08</td><td align="center">0.68</td><td align="center">0.16</td></tr><tr><td align="left"><italic>BRCA2</italic></td><td align="left">2,924</td><td align="center">1,370</td><td align="center">405</td><td align="center">1,645</td><td align="center"><bold>0.91</bold></td><td align="center"><bold>0.84 to 0.99</bold></td><td align="center"><bold>0.028</bold></td><td align="center">1.07</td><td align="center">0.92 to 1.25</td><td align="center">0.40</td><td align="center">0.08</td></tr></tbody></table><table-wrap-foot><p>ER, estrogen receptor; HR, hazard ratio</p></table-wrap-foot></table-wrap><p>Despite the small number of <italic>BRCA2 </italic>ER-negative breast cancers, there was a suggestion that the minor allele of the <italic>PTHLH </italic>SNP rs10771399 is protective for ER-negative breast cancer for <italic>BRCA2 </italic>mutation carriers (HR for ER-negative = 0.78, 95% CI: 0.62 to 1.00, <italic>P</italic>-trend = 0.049), but there was no association with ER-positive breast cancer. There was evidence that SNPs rs10995190 near <italic>ZNF365</italic>, rs865686 at 9q31.2 and rs1011970 near <italic>CDKN2A/B </italic>are associated with ER-positive breast cancer for <italic>BRCA2 </italic>mutation carriers (<italic>P</italic>-trend = 0.043, 0.028 and 0.05 respectively). However, the HR estimates were not significantly different from those for ER-negative breast cancer.</p></sec></sec><sec sec-type="discussion"><title>Discussion</title><p>We have investigated eight novel breast cancer susceptibility loci identified through breast cancer GWAS [<xref ref-type="bibr" rid="B15">15</xref>-<xref ref-type="bibr" rid="B17">17</xref>] for their associations with breast cancer risk for <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers using data from the CIMBA. The estimated per-allele ORs associated with the minor allele of each SNP from the population-based studies varied from 0.85 to 1.15, and only four of the eight SNPs had ORs of less than 0.90 or greater than 1.10 (rs10995190, rs614367, rs865686 and rs10771399) [<xref ref-type="bibr" rid="B15">15</xref>-<xref ref-type="bibr" rid="B17">17</xref>]. For <italic>BRCA1 </italic>mutation carriers, only SNP rs10771399 at 12p11 was associated with the overall risk of breast cancer, whereas SNPs rs10995190 at 10q21, rs1011970 at 9p21, rs865686 at 9q31.2 and rs1292011 at 12q24 were associated with breast cancer risk for <italic>BRCA2 </italic>mutation carriers. The magnitude of the estimated HRs for all these SNPs were consistent with the OR estimates for the risk of breast cancer in the general population. The power to detect associations with SNPs conferring relative risks in the range of 0.90 to 1.10 was limited by our sample size, particularly among <italic>BRCA2 </italic>mutation carriers [<xref ref-type="bibr" rid="B29">29</xref>].</p><p>Based on the HR estimates and associated 95% confidence intervals, given our sample size of <italic>BRCA1 </italic>mutation carriers, it is unlikely that the relative risks for overall <italic>BRCA1 </italic>breast cancer risk are of similar magnitude to those estimated in the general population for SNPs rs10995190 at 10q21 (estimated odds ratio (OR) from the replication stage of the GWAS = 0.76), rs2380205 at 10p15 (OR = 0.94), rs614367 at 11q13 (OR = 1.15), rs1292011 at 12q24 (OR = 0.92) and rs865686 at 9q31.2 (OR = 0.89), since the 95% confidence intervals for the HRs do not include the estimated OR from the population-based studies. Similarly, the HRs for <italic>BRCA2 </italic>breast cancer risk exclude the ORs from the general population for SNPs rs2380205 at 10p15 and rs614367 at 11q13. Taken together, these findings suggest that SNPs rs2380205 at 10p15 and rs614367 at 11q13 do not modify breast cancer risk in either <italic>BRCA1 </italic>or <italic>BRCA2 </italic>mutation carriers. A replication study by BCAC, involving close to 50,000 breast cancer cases and 50,000 controls, found only weak evidence for association of rs2380205 at 10p15 with breast cancer risk in the general population [Lambrechts and Easton personal communication, manuscript submitted] suggesting that the original finding (OR = 0.94, <italic>P </italic>= 5 × 10<sup>-7 </sup>[<xref ref-type="bibr" rid="B15">15</xref>]) may have been a false positive. If this were true, the absence of an association in carriers would be expected. The lack of evidence for an association with the 11q13 SNP rs614367 with <italic>BRCA1 </italic>and <italic>BRCA2 </italic>breast cancer risk is more surprising since the association in the general population is relatively strong and consistently replicated (OR 1.21, 95% CI 1.17 to 1.25 in the recent BCAC analysis [Lambrechts and Easton personal communication, manuscript submitted]). The association in the general population appears to be restricted to ER-positive disease, which would explain the lack of association for <italic>BRCA1 </italic>carriers but not <italic>BRCA2 </italic>carriers. This is perhaps the clearest evidence so far of a departure from a multiplicative interaction between a common susceptibility locus and a <italic>BRCA2 </italic>mutation on the risk of developing breast cancer. The lack of an association in <italic>BRCA1 </italic>carriers for rs1292011 and rs865686 is also consistent with the observation that these associations are stronger for ER-positive disease in the general population [<xref ref-type="bibr" rid="B16">16</xref>]. The absence of an association for <italic>ZNF365 </italic>rs10995190 in <italic>BRCA1 </italic>carriers is more surprising since this association appears to be unrelated to ER status in the general population [Lambrechts and Easton personal communication, manuscript submitted] [<xref ref-type="bibr" rid="B30">30</xref>].</p><p>Of the eight SNPs investigated, the strongest association was found between SNP rs10771399 at 12p11 and breast cancer risk for <italic>BRCA1 </italic>mutation carriers. Other loci previously found to be associated with <italic>BRCA1 </italic>breast cancer risk include the 19p13 and 6q25.1 loci [<xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B9">9</xref>], <italic>TOX3 </italic>and <italic>CASP8 </italic>[<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref>]. Analysis by tumour ER-status revealed that rs10771399 at 12p11 has a stronger association with ER-negative than ER-positive breast cancer for both <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers. The ER-specific HRs were similar for both genes, suggesting that this SNP is primarily associated with ER-negative breast cancer, although results from the general population suggested similar ORs for ER-positive and ER-negative breast cancer (0.87 for ER-positive disease, 0.85 for ER-negative disease [<xref ref-type="bibr" rid="B16">16</xref>]). Interestingly, the association among <italic>BRCA1 </italic>mutation carriers was restricted to those carrying mutations proven or predicted to lead to absence of protein expression (Class 1) with no evidence for an association in carriers of <italic>BRCA1 </italic>mutations likely to generate stable mutant proteins (Class 2) (<italic>P</italic>-diff = 0.03). This observation suggests that the modifying effect of SNP rs10771399 at 12p11 might be attenuated for tumours that retain residual <italic>BRCA1 </italic>function or that retain the capacity to bind to some of its partners. rs10771399 lies in a region at 12p11 that contains <italic>PTHLH </italic>(parathyroid hormone-like hormone isoform 1, also known as <italic>PTHRP - </italic>parathyroid hormone-related protein) and <italic>CCDC91. PTHLH </italic>is a plausible candidate cancer susceptibility gene. It encodes a protein that regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands. The receptor of this hormone, PTHR1, is responsible for most cases of humoral hypercalcemia of malignancy [<xref ref-type="bibr" rid="B31">31</xref>]. It is produced by various types of carcinomas [<xref ref-type="bibr" rid="B32">32</xref>], and is an important factor in the development of bone metastasis [<xref ref-type="bibr" rid="B33">33</xref>].</p><p>We found that SNP rs10995190 <italic>ZNF365 </italic>is associated with <italic>BRCA2 </italic>breast cancer risk. A different SNP (rs16917302) in <italic>ZNF365</italic>, which is only weakly correlated with rs10995190 (pairwise r<sup>2 </sup>is approximately 0.10 in the present sample) was previously identified via a GWAS of breast cancer in <italic>BRCA2 </italic>mutation carriers [<xref ref-type="bibr" rid="B10">10</xref>]. These results suggest that there could be a causal associated variant correlated with both rs10995190 and rs16917302, or alternatively more than one causal disease variant in this locus. SNP rs10995190 has also recently been found to be associated with mammographic density in the general population [<xref ref-type="bibr" rid="B34">34</xref>]. Previous studies found that mammographic density modifies breast cancer risk for <italic>BRCA2 </italic>mutation carriers [<xref ref-type="bibr" rid="B35">35</xref>], raising the possibility that this locus modifies breast cancer risk for <italic>BRCA2 </italic>mutation carriers through its influence on mammographic density. However, mammographic density has also been shown to modify the breast cancer risk for <italic>BRCA1 </italic>carriers, which also makes the absence of association for rs10995190 in <italic>BRCA1 </italic>carriers somewhat surprising. Mammographic density data are not available in the CIMBA sample to test this hypothesis explicitly.</p><p>There was no evidence of association with ovarian cancer risk for <italic>BRCA1 </italic>or <italic>BRCA2 </italic>mutation carriers for any of the SNPs, with the exception of some weak evidence for SNPs rs10771399 and rs614367 for <italic>BRCA1 </italic>carriers. This is not surprising, since all SNPs were selected on the basis of prior evidence of association with breast cancer risk in the general population and none of these SNPs have so far been found to be associated with ovarian cancer in general population through the ongoing GWAS [<xref ref-type="bibr" rid="B36">36</xref>-<xref ref-type="bibr" rid="B38">38</xref>].</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>The per-allele HRs estimated for each of the associated loci in the present report are modest, and in isolation would have only a small impact on the absolute risks of developing breast cancer. However, we have shown previously that modifier SNPs in combination can result in large differences in the absolute risk of developing breast cancer for carriers at the extreme percentiles of the combined SNP distribution [<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B39">39</xref>]. Furthermore, the causal variants underlying these loci may confer larger relative risks. Considering all reported modifying loci by the CIMBA consortium, there are now six loci in total that are associated with breast cancer risk for <italic>BRCA1 </italic>mutation carriers (19p13, 6q25.1, 12p11, <italic>TOX3</italic>, 2q35 and C<italic>ASP8</italic>) and 13 loci which are known to be associated with <italic>BRCA2 </italic>breast cancer risk (<italic>FGFR2, TOX3, MAP3K1, LSP1</italic>, 2q35, <italic>SLC4A7</italic>, 5p12, 1p11.2, <italic>ZNF365, CDKN2A/B</italic>, 9q31.2, 12q24 and <italic>RAD51</italic>). Ongoing GWAS in <italic>BRCA1 </italic>and <italic>BRCA2 </italic>mutation carriers and in the general population are likely to identify further modifier loci and taken together, they may lead to more accurate risk predictions in mutation carriers with implications for clinical management, and to a better understanding of the biology of tumour development in mutation carriers.</p></sec><sec><title>Abbreviations</title><p>BCAC: Breast Cancer Association Consortium; CIMBA: Consortium of Investigators of Modifiers of <italic>BRCA1/2; </italic>ER: estrogen receptor; GWAS: genome-wide association studies; HR: hazard ratio; HWE: Hardy-Weinberg equilibrium; NMD: nonsense-mediated mRNA decay; OR: odds ratio; SNPs: single-nucleotide polymorphism.</p></sec><sec><title>Competing interests</title><p>The authors declare that they have no competing interests.</p></sec><sec><title>Authors' contributions</title><p>ACA, KBK and DFE wrote the manuscript. KBK performed the statistical analysis. ACA supervised the statistical analysis and data management. ACA, GCT and DFE developed the study design. LM and DB are the CIMBA database managers. AL wrote computer programs for the analysis. SH and OMS reviewed, recoded and classified the BRCA1 and BRCA2 mutations in CIMBA. GCT initiated and coordinates CIMBA. PS, JB, XC and YCD performed the genotyping. AJ, SLN, GCT and JS supervised the genotyping of samples. MAC, NL, KH, AL, BA, RR, PK, KN, SD, TR, AJ, JL, KJ, KD, EZ, AO, MD, RA, JB, UH, FBH, TAvO, SV, HEJMH, JW, EBGG, MJL, MK, JMC, MGEMA, JCO, SP, DF, SDE, RP, EF, DGE, FL, CJ, RE, JA, RD, TC, JC, JP, FD, CB, SH, PJM, LW, MTR, AD, HD, AKG, BB, DS, CH, BB, AdP, SM, AC, ML, BBdeP, OC, HS, MF, FP, SFF, IM, SB, MD, AM, MBT, JLH, EMJ, MS, DG, CFS, AFR, MKT, DGK, TvOH, FCN, RBB, MG, TK, VJ, ADC, KO, MP, JK, DC, JH, JB, JF, AET, MM, CO, EI, CI, LT, IB, CL, AT, JDV, SAG, KO, JG, BYK, EO, SHT, PAG, MSB, CMD, EJvR, OD, AK, RKS, BW, CE, AM, ND, NA, SH, DN, SPA, DG, RVM, HD, AG, CS, KK, BF, DS, TC, MdlH, HN, TAM, BL, ABS, SLN, YCD, XW, ZF, VSP, NML, PR, MHG, JTL, ILA, HO, AMM, GG, MT, AMG, UBJ, ABS, TAK, GCT and FJC acquired phenotypic data and DNA samples or designed the centre-specific studies. All authors read and approved the final manuscript for publication.</p></sec><sec sec-type="supplementary-material"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="S1"><caption><title>Additional file 1</title><p><bold>Supplementary tables and figures</bold>. Table S1 List of local ethics committees that granted approval for the access and use of the data in current study. Supplementary figure 1 Forest plot of the country-specific per-allele HR estimates for breast cancer for <italic>BRCA1 </italic>mutation carriers. Supplementary figure 2 Forest plot of the country-specific per-allele HR estimates for breast cancer for <italic>BRCA2 </italic>mutation carriers.</p></caption><media xlink:href="bcr3121-S1.DOCX"><caption><p>Click here for file</p></caption></media></supplementary-material></sec></body><back><sec><title>Acknowledgements</title><p>This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175), from the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. This research was also supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow, GCT is a NHMRC Senior Principal Research Fellow, J.S. is Chairholder of the Canada Research Chair in Oncogenetics.</p><sec><title>Study specific</title><sec><title>Baltic Familial Breast and Ovarian Cancer Consortium</title><p>We acknowledge the Genome Database of Latvian Population, Latvian Biomedical</p><p>Research and Study Centre and Ramunas Janavicius (Vilnius University Hospital Santariskiu Clinics, Lithuania) for data and DNA samples for BFBOCC. The work was supported in part by a grant from the European Social Fund Nr.2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016.</p><p><italic>BMBSA w</italic>as supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg.</p></sec><sec><title>Breast Cancer Family Registry (BCFR)</title><p>This work was supported by the National Cancer Institute, National Institutes of Health 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), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center) (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). Samples from the FCCC, HCI and CPIC 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 centres in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR.</p></sec><sec><title>CNIO</title><p>The research leading to these results has been partially funded by Mutua Madrileña Foundation, "Red de Investigación en Cáncer RD06/0020/1160" and Spanish Ministry of Science and Innovation (FIS PI08 1120 and SAF2010-20493).</p></sec><sec><title>Copenhagen Breast Cancer Study (CBCS)</title><p>We would like to thank Bent Ejlertsen for clinical data and acknowledge the NEYE foundation for financial support.</p></sec><sec><title>Deutsches Krebsforschungszentrum (DKFZ) study</title><p>The DKFZ study was supported by the DKFZ.</p></sec><sec><title>Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE)</title><p>Douglas F. Easton is the PI of the study. EMBRACE Collaborating Centres are: Coordinating Centre, Cambridge: Susan Peock, Debra Frost, Steve D. Ellis, Elena Fineberg, Radka Platte, Clare Oliver. North of Scotland Regional Genetics Service, Aberdeen: Zosia Miedzybrodzka, Helen Gregory. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Kai-ren Ong, Jonathan Hoffman. South West Regional Genetics Service, Bristol: Alan Donaldson, Margaret James. East Anglian Regional Genetics Service, Cambridge: Joan Paterson, Sarah Downing, Amy Taylor. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin and National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Sarah Drummond. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman, Kathryn Hill. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson, Eshika Haque, Ed Tobias, Alexis Duncan. South East Thames Regional Genetics Service, Guy's Hospital London: Louise Izatt, Chris Jacobs, Caroline Langman. North West Thames Regional Genetics Service, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Julian Adlard, Gemma Serra-Feliu. Cheshire & Merseyside Clinical Genetics Service, Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Jane Taylor. North East Thames Regional Genetics Service, NE Thames, London: Lucy Side, Alison Male, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber, Irene Jobson. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah Smalley. EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles is supported by Cancer Research UK Grant C5047/A8385.</p></sec><sec><title>GEORGETOWN</title><p>CI received support from the Familial Cancer Registry and the Tissue Culture Shared Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure.</p></sec><sec><title>Gynecologic Oncology Group (GOG)</title><p>This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), and to the GOG Statistical and Data Center (CA 37517 and CA 101165). We thank the investigators of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). GOG's participation was sponsored by GOG's Cancer Prevention and Control Committee, and supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program - COPTRG) NCI programs.</p></sec><sec><title>Hospital Clinico San Carlos (HCSC)</title><p>The HCSC study was partially supported by Instituto de Salud Carlos III; RD06/0020/0021. We wish to thank Dr. Pedro Perez-Segura and Dr. Atocha Romero for their contribution to this study.</p></sec><sec><title>The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)</title><p>HEBON Collaborating Centres: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: F.B.L. Hogervorst, S. Verhoef, M. Verheus, L.J. van 't Veer, F.E. van Leeuwen, M.A. Rookus; Erasmus Medical Center, Rotterdam, NL: M. Collée, A.M.W. van den Ouweland, A. Jager, M.J. Hooning, M.M.A. Tilanus-Linthorst, C. Seynaeve; Leiden University Medical Center, NL, Leiden: C.J. van Asperen, J.T. Wijnen, M.P. Vreeswijk, R.A. Tollenaar, P. Devilee; Radboud University Nijmegen Medical Center, Nijmegen, NL: M.J. Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht, NL: M.G. Ausems, R.B. van der Luijt; Amsterdam Medical Center, NL: C.M. Aalfs, T.A. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, Maastricht, NL: E.B. Gomez-Garcia, C.E. van Roozendaal, Marinus J. Blok, B. Caanen; University Medical Center Groningen University, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756 and the ZonMW grant 91109024.</p></sec><sec><title>Helsinki Breast Cancer Study (HEBCS)</title><p>HEBCS acknowledge Drs. Kristiina Aittomäki, Kirsimari Aaltonen and Carl Blomqvist and Tuomas Heikkinen and research nurse Irja Erkkilä for their help with the patient data and samples. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation.</p></sec><sec><title>ICO</title><p>Contract grant sponsor: Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488 and 2009SGR290.</p></sec><sec><title>ILUH</title><p>The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.</p></sec><sec><title>INHERIT</title><p>We would like to thank Stéphane Dubois, Dr Martine Dumont, Martine Tranchant (Cancer Genomics Laboratory, CRCHUQ) for sample management and skillful technical assistance, Sylvie Desjardins and Marc-André Rodrigue (Plateforme de séquençage et de génotypage des génome du CRCHUL/CHUQ) for iPLEX genotyping and Pascal Belleau for data quality control analyses.</p></sec><sec><title>Istituto Oncologico Veneto Hereditary Breast and Ovarian Cancer Study (IOVHBOCS)</title><p>This study was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) and "Ministero della Salute" ("Progetto Tumouri Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9")</p></sec><sec><title>kConFab</title><p>We wish to 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. ABS is funded by an NHMRC Senior Research Fellowship.</p></sec><sec><title>Memorial Sloan-Kettering Cancer Center (MSKCC)</title><p>We acknowledge the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative.</p></sec><sec><title>National Cancer Institute (NCI)</title><p>The research of Drs. Greene and Loud was supported by the Intramural Research Program of the US National Cancer Institute at the National Institutes of Health, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD.</p></sec><sec><title>N.N. Petrov Institute of Oncology (NNPIO)</title><p>This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) the Federal Agency for Science and Innovations (contract 16.512.11.2237) and through a Royal Society International Joint grant (JP090615).</p><p>The <italic>Hong Kong Hereditary Breast Cancer Family Registry </italic>thank Dr. Ellen Li Charitable Foundation for their support</p></sec><sec><title>Hungarian Breast and Ovarian Cancer Study (HUNBOCS)</title><p>The study was supported by Norwegian EEA Financial Mechanism (HU0115/NA/2008-3/ÖP-9) and by Hungarian Research Grant KTIA-OTKA (CK-80745).</p></sec><sec><title>Ohio State University Clinical Cancer Genetics (OSU-CCG)</title><p>Leigha Senter and Kevin Sweet were instrumental in accrual of study participants, ascertainment of medical records and database management. We thank the Human Genetics Sample Bank for preparation of samples. This study was supported by the Ohio State University Comprehensive Cancer Center.</p></sec><sec><title>Ontario Cancer Genetics Network Study (OCGN)</title><p>This work was supported by Cancer Care Ontario, the "CIHR Team in Familial Risks of Breast Cancer" program, and the US National Cancer Institute, National Institutes of Health under RFA # CA- 06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. We wish to thank Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study.</p></sec><sec><title>Beckman Research Institute of City of Hope (BRICOH)</title><p>The study was supported by the National Institutes of Health (R01 CA74415 to SLN)) and the Morris and Horowitz Families Endowment.</p></sec><sec><title>SWE-BRCA</title><p>SWE-BRCA collaborators: Per Karlsson, Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Marie Stenmark-Askmalm and Sigrun Liedgren, Linköping University Hospital; Åke Borg, Niklas Loman, Håkan Olsson, Maria Soller, Helena Jernström, Katja Harbst and Karin Henriksson, Lund University Hospital; Annika Lindblom, Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna Rantala, Stockholm, Karolinska University Hospital; Beatrice Melin, Henrik Grönberg, Eva-Lena Stattin and Monica Emanuelsson, Umeå University Hospital; Hans Ehrencrona, Richard Rosenquist and Niklas Dahl, Uppsala University Hospital.</p></sec><sec><title>U.K. and Gilda Radner Familial Ovarian Cancer Registry (UKGRFOCR)</title><p>UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Paul Pharoah, Susan Ramus, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We would like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Kirsten Moysich and Lara Sucheston (Department of Cancer Prevention and Control).</p></sec><sec><title>University of Kansas Medical Center (KUMC)</title><p>We thank Ms. JoEllen Weaver for her help collecting patient data and samples. AKG was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. 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