Article
Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
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- (3) Wellcome Sanger Institute, grid.10306.34
- (4) University of Cambridge, grid.5335.0
- (5) Cyprus Institute of Neurology and Genetics, grid.417705.0
- (6) QIMR Berghofer Medical Research Institute, grid.1049.c
- (7) University of Washington, grid.34477.33
- (8) Harvard University, grid.38142.3c
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- (11) Massachusetts Institute of Technology, grid.116068.8
- (12) Academic Medical Center, grid.5650.6
- (13) Johns Hopkins University, grid.21107.35
- (14) Chapel Allerton Hospital, grid.413818.7
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- (17) Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
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- (24) Institute of Clinical Molecular Biology / Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany
- (25) Queen's University, grid.410356.5
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- (31) McGill University and Génome Québec Innovation Centre, grid.411640.6
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- (34) Centre Léon Bérard, grid.418116.b
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- (36) University of Iceland, grid.14013.37
- (37) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (38) Spanish National Cancer Research Centre, grid.7719.8
- (39) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
- (40) Institute of Biochemistry and Genetics of Ufa Scientific Centre, grid.429129.5
- (41) City Of Hope National Medical Center, grid.410425.6
- (42) Université Clermont Auvergne, INSERM, U1240, Imagerie Moléculaire et Stratégies Théranostiques, Centre Jean Perrin, Clermont-Ferrand, France
- (43) Maastricht University Medical Centre, grid.412966.e
- (44) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (45) International Epidemiology Institute, grid.419344.f
- (46) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- (47) Flanders Institute for Biotechnology, grid.11486.3a
- (48) KU Leuven, grid.5596.f
- (49) Vejle Sygehus, grid.417271.6, Southern Denmark Region
- (50) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (51) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (52) University of Copenhagen, grid.5254.6, KU
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- (55) Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
- (56) Karolinska Institute, grid.4714.6
- (57) University of Tübingen, grid.10392.39
- (58) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
- (59) Institut Gustave Roussy, grid.14925.3b
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- (63) Simon Fraser University, grid.61971.38
- (64) BC Cancer Agency, grid.248762.d
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- (72) University of Santiago de Compostela, grid.11794.3a
- (73) Complejo Hospitalario Universitario de Santiago, grid.411048.8
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- (77) Institute Curie, grid.418596.7
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- (92) University of Glasgow, grid.8756.c
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- (94) Ludwig Maximilian University of Munich, grid.5252.0
- (95) University of Pretoria, grid.49697.35
- (96) London School of Hygiene & Tropical Medicine, grid.8991.9
- (97) University of Southampton, grid.5491.9
- (98) University of Westminster, grid.12896.34
- (99) University of Münster, grid.5949.1
- (100) Royal Marsden NHS Foundation Trust, grid.5072.0
- (101) Skåne University Hospital, grid.411843.b
- (102) Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- (103) Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (104) Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
- (105) Leipzig University, grid.9647.c
- (106) Centre Georges François Leclerc, grid.418037.9
- (107) Centre Hospitalier Regional Universitaire De Dijon, grid.31151.37
- (108) University of California, Los Angeles, grid.19006.3e
- (109) University of Edinburgh, grid.4305.2
- (110) University Medical Center Hamburg-Eppendorf, grid.13648.38
- (111) Institute of Cancer Research, grid.18886.3f
- (112) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (113) McGill University, grid.14709.3b
- (114) Tel Aviv University, grid.12136.37
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- (116) Curtin University, grid.1032.0
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- (118) University of North Carolina at Chapel Hill, grid.10698.36
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- (120) University of Würzburg, grid.8379.5
- (121) University Hospital of Heraklion, grid.412481.a
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- (123) University of Kansas Medical Center, grid.412016.0
- (124) University of Utah, grid.223827.e
- (125) Department of Obstetrics and Gynecology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, USA
- (126) National Institutes of Health, grid.94365.3d
- (127) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
- (128) Pomeranian Medical University, grid.107950.a
- (129) Centre Hospitalier de l’Université de Montréal, grid.410559.c
- (130) Medical University of Vienna, grid.22937.3d
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- (133) University of Southern California, grid.42505.36
- (134) University of Massachusetts Amherst, grid.266683.f
- (135) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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- (137) University of Eastern Finland, grid.9668.1
- (138) Institute of Genetic Medicine, Centre for Life, Newcastle-upon-Tyne Hospitals NHS Trust, Newcastle-upon-Tyne, UK
- (139) University of Western Australia, grid.1012.2
- (140) University College London, grid.83440.3b
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- (144) Institute of Oncology NN Petrov, grid.465337.0
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- (150) Aarhus University Hospital, grid.154185.c, Central Denmark Region
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- (153) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
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- (159) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
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- (163) University of Oslo, grid.5510.1
- (164) Odense University Hospital, grid.7143.1, Southern Denmark Region
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- (170) Clalit National Cancer Control Center, Haifa, Israel
- (171) Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain
- (172) University of Hawaii at Manoa, grid.410445.0
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- (196) West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK
- (197) Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- (198) University of New Mexico, grid.266832.b
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- (234) Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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- (240) Prince of Wales Hospital, grid.415193.b
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- (242) Frauenklinik der Stadtklinik Baden Baden, Baden Baden, Germany
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- (250) Royal Women's Hospital, grid.416259.d
- (251) Sapienza University of Rome, grid.7841.a
- (252) Department of Oncology, South General Hospital, Stockholm, Sweden
- (253) Technical University of Munich, grid.6936.a
Description
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
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