Letter | Published:

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor–negative breast cancer in the general population

Nature Genetics volume 42, pages 885892 (2010) | Download Citation

Abstract

Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (Ptrend = 2.3 × 10−9 to Ptrend = 3.9 × 10−7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17–1.35; rs2363956 HR = 0.84, 95% CI 0.80–0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor–negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75–0.92, Ptrend = 0.0003) and an association with estrogen receptor–positive disease in the opposite direction (OR = 1.07, 95% CI 1.01–1.14, Ptrend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 × 10−7 to Ptrend = 8 × 10−5; rs2363956 per-allele OR = 0.80, 95% CI 0.74–0.87, Ptrend = 1.1 × 10−7).

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Acknowledgements

Financial support for this study was provided by the Breast Cancer Research Foundation (BCRF), Susan G. Komen for the Cure and US National Institutes of Health grant CA128978 to F.J.C. and by Cancer Research UK to D.F.E. and A.C.A. A.C.A. is a Cancer Research UK Senior Cancer Research Fellow and D.F.E. is a Cancer Research UK Principal Research Fellow. The authors thank Cancer Genetic Markers of Susceptability (CGEMS) and Wellcome Trust Case Control Consortium (WTCCC) for provision of genotype data from controls. Study specific acknowledgments listed in Supplementary Note.

Author information

Affiliations

  1. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Antonis C Antoniou
    • , Lesley McGuffog
    • , Jonathan Morrison
    • , Christiana Kartsonaki
    • , Daniel Barrowdale
    • , Susan Peock
    • , Margaret Cook
    • , Clare Oliver
    • , Debra Frost
    • , Fiona Blows
    • , Kristy Driver
    • , Alison Dunning
    • , Paul P D Pharoah
    •  & Douglas F Easton
  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

    • Xianshu Wang
    • , Lucia Guidugli
    • , Csilla I Szabo
    •  & Fergus J Couch
  3. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

    • Zachary S Fredericksen
    • , Robert Tarrell
    • , Timothy Lesnick
    • , Jeanette Eckel-Passow
    • , Celine Vachon
    •  & V Shane Pankratz
  4. Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, Lyon, France.

    • Olga M Sinilnikova
    •  & Sophie Giraud
  5. Equipe labellisée LIGUE 2008, UMR5201 CNRS, Centre Léon Bérard, Université de Lyon, Lyon, France.

    • Olga M Sinilnikova
    •  & Sylvie Mazoyer
  6. Queensland Institute of Medical Research, Brisbane, Australia.

    • Sue Healey
    • , Maya Ghoussaini
    • , Amanda B Spurdle
    • , Helene Holland
    •  & Georgia Chenevix-Trench
  7. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.

    • Diana Eccles
    • , Sue M Gerty
    •  & William Tapper
  8. Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals National Health Service (NHSFT) Foundation Trust, Manchester, UK.

    • D Gareth Evans
  9. Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.

    • Ros Eeles
  10. Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK.

    • Louise Izatt
  11. Yorkshire Regional Genetics Service, Leeds, UK.

    • Carol Chu
  12. Institute of Human Genetics, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.

    • Fiona Douglas
  13. Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK.

    • Joan Paterson
  14. INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes, Paris, France.

    • Dominique Stoppa-Lyonnet
    •  & Claude Houdayer
  15. CNRS UMR5558, Université Lyon 1, Lyon, France.

    • Christine Lasset
  16. Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France.

    • Christine Lasset
  17. Genetics Department, Institut de Cancérologie Gustave Roussy, Villejuif, France.

    • Audrey Remenieras
  18. Consultation de Génétique, Département de Médecine, Institut de Cancérologie Gustave Roussy, Villejuif, France.

    • Olivier Caron
  19. Centre François Baclesse, Caen, France.

    • Agnès Hardouin
    •  & Pascaline Berthet
  20. GEMO study, Cancer Genetics Network 'Groupe Génétique et Cancer', Fédération Nationale des Centres de Lutte Contre le Cancer, Paris, France.

  21. Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands.

    • Frans B L Hogervorst
  22. Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

    • Matti A Rookus
  23. Department of Medical Oncology, Rotterdam Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Agnes Jager
  24. Department of Clinical Genetics, Rotterdam Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Ans van den Ouweland
  25. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    • Nicoline Hoogerbrugge
  26. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

    • Rob B van der Luijt
  27. Department of Clinical Genetics, Vrije Universiteit (VU) Medical Center, Amsterdam, The Netherlands.

    • Hanne Meijers-Heijboer
  28. Department of Clinical Genetics, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.

    • Encarna B Gómez García
  29. HEBON, Hereditary Breast and Ovarian Cancer Research Group, The Netherlands.

  30. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

    • Peter Devilee
  31. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

    • Peter Devilee
  32. Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.

    • Maaike P G Vreeswijk
  33. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    • Jan Lubinski
    • , Anna Jakubowska
    • , Jacek Gronwald
    • , Tomasz Huzarski
    • , Tomasz Byrski
    • , Bohdan Górski
    •  & Cezary Cybulski
  34. kConFab, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia.

  35. Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah, USA.

    • David E Goldgar
  36. Cancer Prevention Institute of California, Stanford University School of Medicine, Stanford, California, USA.

    • Esther M John
  37. The University of Melbourne, Melbourne, Australia.

    • John L Hopper
    •  & Melissa Southey
  38. Huntsman Cancer Institute, University of Utah Health Sciences Centre, Salt Lake City, Utah, USA.

    • Saundra S Buys
  39. Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

    • Mary B Daly
    •  & Andrew K Godwin
  40. Columbia University, New York, New York, USA.

    • Mary-Beth Terry
  41. Centre of Familial Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology, University of Cologne, Cologne, Germany.

    • Rita K Schmutzler
    •  & Barbara Wappenschmidt
  42. Centre for Integrated Oncology (CIO), University of Cologne, Cologne, Germany.

    • Rita K Schmutzler
    •  & Barbara Wappenschmidt
  43. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.

    • Christoph Engel
  44. Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.

    • Alfons Meindl
  45. Institute of Human Genetics, University of Muenster, Muenster, Germany.

    • Sabine Preisler-Adams
  46. Department of Obstetrics and Gynaecology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University, Kiel, Germany.

    • Norbert Arnold
  47. Department of Obstetrics and Gynaecology, Division of Molecular Genetics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Dusseldorf, Germany.

    • Dieter Niederacher
  48. Institute of Human Genetics, Division of Molecular Diagnostics, University Heidelberg, Heidelberg, Germany.

    • Christian Sutter
  49. University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Susan M Domchek
    • , Katherine L Nathanson
    •  & Timothy Rebbeck
  50. Baylor-Charles A. Sammons Cancer Center, Dallas, Texas, USA.

    • Joanne L Blum
  51. Gynecology Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York, USA.

    • Marion Piedmonte
  52. Northshore University Health System, Evanston Northwestern Healthcare, Evanston, Illinois, USA.

    • Gustavo C Rodriguez
  53. Tufts University, New England Medical Center, Boston, Massachusetts, USA.

    • Katie Wakeley
  54. University of North Carolina, Chapel Hill, North Carolina, USA.

    • John F Boggess
  55. St. Elizabeth Medical Center, Edgewood, Kentucky, USA.

    • Jack Basil
  56. New York University School of Medicine, New York, New York, USA.

    • Stephanie V Blank
  57. The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.

    • Eitan Friedman
    • , Yael Laitman
    •  & Roni Milgrom
  58. Oncology Institute, Sheba Medical Center, Tel-Hashomer, Israel.

    • Bella Kaufman
  59. Ontario Cancer Genetics Network, Cancer Care Ontario, Toronto, Ontario, Canada.

    • Irene L Andrulis
    •  & Gord Glendon
  60. Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

    • Irene L Andrulis
    •  & Hilmi Ozcelik
  61. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

    • Irene L Andrulis
    •  & Kenneth Offit
  62. Clinical Genetics Service, Memorial Hospital, New York, New York, USA.

    • Tomas Kirchhoff
    •  & Joseph Vijai
  63. Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Tomas Kirchhoff
    •  & Joseph Vijai
  64. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York, USA.

    • Mia M Gaudet
  65. Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, New York, New York, USA.

    • Mia M Gaudet
  66. Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.

    • David Altshuler
    •  & Candace Guiducci
  67. SWE-BRCA, Swedish Breast Cancer Study, Sweden.

  68. Department of Oncology, Lund University, Lund, Sweden.

    • Niklas Loman
    •  & Katja Harbst
  69. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

    • Johanna Rantala
  70. Department of Genetics and Pathology Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

    • Hans Ehrencrona
  71. Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.

    • Anne-Marie Gerdes
  72. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

    • Mads Thomassen
  73. Department of Clinical Genetics, Aalborg and Aarhus University Hospital, Aaarhus, Denmark.

    • Lone Sunde
  74. Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori (INT), Milan, Italy.

    • Paolo Peterlongo
    •  & Paolo Radice
  75. IFOM, Fondazione Istituto Fondazione Italiana per la Ricera sul Cancro (FIRC) di Oncologia Molecolare, Milan, Italy.

    • Paolo Peterlongo
    •  & Paolo Radice
  76. Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.

    • Siranoush Manoukian
  77. Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.

    • Bernardo Bonanni
    •  & Miguel de la Hoya
  78. Division of Experimental Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy.

    • Alessandra Viel
  79. Hospital Clinico San Carlos, Madrid, Spain.

    • Trinidad Caldes
  80. Department of Obstetrics/Gynocology, Medical University of Vienna, Vienna, Austria.

    • Christian F Singer
    •  & Anneliese Fink-Retter
  81. Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

    • Mark H Greene
    • , Phuong L Mai
    •  & Jennifer T Loud
  82. Medical Genetics, Mayo Clinic Rochester, Rochester, Minnesota, USA.

    • Noralane M Lindor
  83. Department of Clinical Biochemistry, Copenhagen University Hospital, Copenhagen, Denmark.

    • Thomas V O Hansen
    •  & Finn C Nielsen
  84. Hereditary Cancer Program, Catalan Institute of Oncology, Gran Via de l'Hospitalet, Barcelona, Spain.

    • Ignacio Blanco
    •  & Conxi Lazaro
  85. Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

    • Judy Garber
  86. Department of Gynaecological Oncology, University College London, Elizabeth Garrett Anderson (EGA) Institute for Women's Health, London, UK.

    • Susan J Ramus
    •  & Simon A Gayther
  87. Women's College Research Institute, Toronto, Ontario, Canada.

    • Catherine Phelan
  88. Department of Epidemiology and Genetics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.

    • Stephen Narod
  89. MOD SQUAD, Modifier Study of Quantitative Effects on Disease, Madrid, Spain.

  90. Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain.

    • Javier Benitez
    •  & Ana Osorio
  91. Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland.

    • Heli Nevanlinna
    •  & Tuomas Heikkinen
  92. Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa, Pisa University Hospital, Pisa, Italy.

    • Maria A Caligo
  93. Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

    • Mary S Beattie
  94. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

    • Mary S Beattie
  95. Cancer Risk Program, Helen Diller Family Cancer Center, University of California, San Francisco, San Francisco, California, USA.

    • Mary S Beattie
  96. German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Ute Hamann
    •  & Asta Försti
  97. Istituto Oncologico Veneto-IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy.

    • Marco Montagna
    •  & Cinzia Casella
  98. Department of Population Sciences, The Beckman Research Institute of the City of Hope, Duarte, California, USA.

    • Susan L Neuhausen
  99. Women's Cancer Research Institute at the Samuel Oschin Cancer Institute, Division of Gynecologic Oncology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Beth Y Karlan
  100. Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.

    • Beth Y Karlan
  101. Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

    • Nadine Tung
  102. Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, Division of Human Genetics, Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA.

    • Amanda E Toland
  103. Division of Clinical Cancer Genetics, City of Hope Cancer Center, Duarte, California, USA.

    • Jeffrey Weitzel
  104. University of Chicago Medical Center, Chicago, Illinois, USA.

    • Olofunmilayo Olopade
  105. Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Quebec, Québec City, Quebec, Canada.

    • Jacques Simard
    •  & Penny Soucy
  106. Université Laval, Centre de recherche du Centre Hospitalier Universitaire de Quebéc (CHUQ), Québec City, Quebec, Canada.

    • Jacques Simard
  107. Northshore University Health System, Evanston, Illinois, USA.

    • Wendy S Rubinstein
  108. Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.

    • Adalgeir Arason
  109. QIMR GWAS Collective, Queensland Institute of Medical Research, Brisbane, Australia.

    • Gad Rennert
  110. Clalit Health Services National Cancer Control Center, Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.

    • Nicholas G Martin
    •  & Grant W Montgomery
  111. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.

    • Jenny Chang-Claude
  112. Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.

    • Dieter Flesch-Janys
  113. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.

    • Hiltrud Brauch
  114. University Tübingen, Tübingen, Germany.

    • Hiltrud Brauch
  115. GENICA, Gene Environment Interaction and Breast Cancer in Germany, Melbourne, Australia.

  116. Melbourne Collaborative Cohort Study (MCCS), Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia.

    • Gianluca Severi
    •  & Laura Baglietto
  117. Institute for Cancer Studies, Department of Oncology, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.

    • Angela Cox
  118. Academic Unit of Pathology, Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.

    • Simon S Cross
  119. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

    • Penelope Miron
  120. Molecular Diagnostics Laboratory Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research 'Demokritos', Athens, Greece.

    • Drakoulis Yannoukakos
  121. Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

    • George Fountzilas
  122. Hellenic Cooperative Oncology Group, Greece.

    • George Fountzilas
  123. University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, Los Angeles, California, USA.

    • Peter A Fasching
  124. University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen, Germany.

    • Matthias W Beckmann
  125. Cancer Research UK Epidemiology and Genetics Group, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

    • Isabel dos Santos Silva
    •  & Julian Peto
  126. Vesalius Research Center (VRC), VIB, Leuven, Belgium.

    • Diether Lambrechts
  127. Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium.

    • Robert Paridaens
  128. Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.

    • Thomas Rüdiger
  129. Center for Primary Health Care Research, University of Lund, Lund, Sweden.

    • Asta Försti
  130. Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland.

    • Robert Winqvist
    •  & Katri Pylkäs
  131. Department of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.

    • Robert B Diasio
    •  & Adam M Lee
  132. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson

Consortia

  1. EMBRACE

    1. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge

    A full list of members is provided in the Supplementary Note.

  2. GEMO Study Collaborators

    1. GEMO study, Cancer Genetics Network 'Groupe Génétique et Cancer', Fédération Nationale des Centres de Lutte Contre le Cancer

    A full list of members is provided in the Supplementary Note.

  3. HEBON

    1. HEBON, Hereditary Breast and Ovarian Cancer Research Group

    A full list of members is provided in the Supplementary Note.

  4. kConFab

    1. kConFab, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Centre

    A full list of members is provided in the Supplementary Note.

  5. SWE-BRCA

    1. SWE-BRCA, Swedish Breast Cancer Study

    A full list of members is provided in the Supplementary Note.

  6. MOD SQUAD

    1. MOD SQUAD, Modifier Study of Quantitative Effects on Disease

    A full list of members is provided in the Supplementary Note.

  7. GENICA

    1. GENICA, Gene Environment Interaction and Breast Cancer in Germany

    A full list of members is provided in the Supplementary Note.

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Contributions

F.J.C., A.C.A. and D.F.E. designed the study and obtained financial support. G.C.-T. founded CIMBA in order to provide the infrastructure for the BRCA1 GWAS. F.J.C. and X.W. coordinated collection of samples. A.C.A. directed the statistical analysis. D.F.E. advised on the statistical analysis. C.K., Z.S.F. and T.L. carried out analyses. Z.S.F., R.T., J.M., L.M. and D.B. provided bioinformatics and database support. F.J.C., H. Hakonarson and X.W. directed the genotyping of the BRCA1 carrier and triple-negative samples. M.G. directed the genotyping of the UK case-control samples. A.C.A., F.J.C. and D.F.E. drafted the manuscript. F.J.C. was the overall project leader.

O.M.S. and S.H. coordinated the BRCA1 mutation classification. T.K., J.V., M.M.G., D.A. and C.G. were involved in the BRCA2 GWAS genotyping and coordination. K.O. led the BRCA2 GWAS.

S.P., M.C., C.O., D.F., D.E., D.G.E., R.E., L.I., C.C., F.D., J.P., O.M.S., D.S.-L., C.H., S.M., S.G., C.L., A.R., O.C., A.H., P.B., F.B.L.H., M.A.R., A.J., A.v.d.O., N.H., R.B.v.d.L., H.M.-H., E.B.G.G., P.D., M.P.G.V., J.L., A.J., J.G., T.H., T.B., B.G., C.C., A.B.S., H.H., D.E., E.M.J., J.L.H., M.S., S.S.B., M.B.D., M.-B.T., R.K.S., B.W., C.E., A.M., S.P.-A., N.A., D.N., C.S., S.M.D., K.L.N., T.R., J.L.B., M.P., G.C.R., K.W., J.F.B., J.B., S.V.B., E.F., B.K., Y.L., R.M., I.L.A., G.G., H.O., N.L., K.H., J.R., H.E., A.-M.G., M.T., L.S., P.P., S.M., B.B., A.V., P.R., T.C., M.d.l.H., C.F.S., A.F.-R., M.H.G., P.L.M., J.T.L., L.G., N.M.L., T.V.O.H., F.C.N., I.B., C.L., J.G., S.J.R., S.A.G., C.P., S.N., C.I.S., J.B., A.O., H.N., T.H., M.A.C., M.S.B., U.H., A.K.G., M.M., C.C., S.L.N., B.Y.K., N.T., A.E.T., J.W., O.O., J.S., P.S., W.S.R., A.A. and G.R. collected data and samples on BRCA1 and or BRCA2 mutation carriers.

N.G.M., G.W.M., J.C.-C., D.F.-J., H.B., G.S., L.B., A.C., S.S.C., P.M., S.M.G., W.T., D.Y., G.F., P.A.F., M.W.B., I.d.S.S., J.P., D.L., R.P., T.R., A.F., R.W., K.P., R.B.D., A.M.L., J.E.-P., C.V., F.B., K.D., A.D. and P.P.D.P. collected data and samples for the TNBCC case-control and/or the SEARCH studies.

All authors provided critical review of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Fergus J Couch.

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    Supplementary Text and Figures

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DOI

https://doi.org/10.1038/ng.669

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