Couch FJ 1 , Kuchenbaecker KB 2 , Michailidou K 2 , Mendoza-Fandino GA 3 , Nord S 4 , Lilyquist J 5 Show all authors , Olswold C 5 , Hallberg E 5 , Agata S 6 , Ahsan H 7 , Aittomäki K 8 , Ambrosone C 9 , Andrulis IL 10 , Anton-Culver H 11 , Arndt V 12 , Arun BK 13 , Arver B 14 , Barile M 15 , Barkardottir RB 16 , Barrowdale D 2 , Beckmann L 17 , Beckmann MW 18 , Benitez J 19 , Blank SV 20 , Blomqvist C 21 , Bogdanova NV 22 , Bojesen SE 23 , Bolla MK 2 , Bonanni B 15 , Brauch H 24 , Brenner H 12 , Burwinkel B 25 , Buys SS 26 , Caldes T 27 , Caligo MA 28 , Canzian F 29 , Carpenter J 30 , Chang-Claude J 31 , Chanock SJ 32 , Chung WK 33 , Claes KB 34 , Cox A 35 , Cross SS 36 , Cunningham JM 1 , Czene K 37 , Daly MB 38 , Damiola F 39 , Darabi H 37 , de la Hoya M 27 , Devilee P 40 , Diez O 41 , Ding YC 42 , Dolcetti R 43 , Domchek SM 44 , Dorfling CM 45 , Dos-Santos-Silva I 46 , Dumont M 47 , Dunning AM 48 , Eccles DM 49 , Ehrencrona H 50 , Ekici AB 51 , Eliassen H 52 , Ellis S 2 , Fasching PA 18 , Figueroa J 32 , Flesch-Janys D 53 , Försti A 54 , Fostira F 55 , Foulkes WD 56 , Friebel T 57 , Friedman E 58 , Frost D 2 , Gabrielson M 37 , Gammon MD 59 , Ganz PA 60 , Gapstur SM 61 , Garber J 62 , Gaudet MM 61 , Gayther SA 63 , Gerdes AM 64 , Ghoussaini M 48 , Giles GG 65 , Glendon G 10 , Godwin AK 66 , Goldberg MS 67 , Goldgar DE 68 , González-Neira A 69 , Greene MH 70 , Gronwald J 71 , Guénel P 72 , Gunter M 73 , Haeberle L 18 , Haiman CA 74 , Hamann U 75 , Hansen TV 76 , Hart S 5 , Healey S 77 , Heikkinen T 25 , Henderson BE 74 , Herzog J 78 , Hogervorst FB 79 , Hollestelle A 80 , Hooning MJ 81 , Hoover RN 32 , Hopper JL 82 , Humphreys K 37 , Hunter DJ 83 , Huzarski T 71 , Imyanitov EN 84 , Isaacs C 85 , Jakubowska A 71 , James P 86 , Janavicius R 87 , Jensen UB 88 , John EM 89 , Jones M 90 , Kabisch M 75 , Kar S 48 , Karlan BY 91 , Khan S 92 , Khaw KT 93 , Kibriya MG 7 , Knight JA 94 , Ko YD 95 , Konstantopoulou I 55 , Kosma VM 96 , Kristensen V 4 , Kwong A 97 , Laitman Y 58 , Lambrechts D 98 , Lazaro C 99 , Lee E 100 , Le Marchand L 101 , Lester J 91 , Lindblom A 102 , Lindor N 103 , Lindstrom S 104 , Liu J 105 , Long J 106 , Lubinski J 71 , Mai PL 70 , Makalic E 82 , Malone KE 107 , Mannermaa A 96 , Manoukian S 108 , Margolin S 14 , Marme F 25 , Martens JW 80 , McGuffog L 2 , Meindl A 109 , Miller A 110 , Milne RL 65 , Miron P 111 , Montagna M 6 , Mazoyer S 39 , Mulligan AM 112 , Muranen TA 25 , Nathanson KL 44 , Neuhausen SL 42 , Nevanlinna H 92 , Nordestgaard BG 23 , Nussbaum RL 113 , Offit K 114 , Olah E 115 , Olopade OI 116 , Olson JE 5 , Osorio A 19 , Park SK 117 , Peeters PH 118 , Peissel B 108 , Peterlongo P 119 , Peto J 46 , Phelan CM 3 , Pilarski R 120 , Poppe B 34 , Pylkäs K 121 , Radice P 122 , Rahman N 123 , Rantala J 124 , Rappaport C 125 , Rennert G 126 , Richardson A 127 , Robson M 114 , Romieu I 128 , Rudolph A 31 , Rutgers EJ 129 , Sanchez MJ 130 , Santella RM 131 , Sawyer EJ 132 , Schmidt DF 82 , Schmidt MK 129 , Schmutzler RK 133 , Schumacher F 74 , Scott R 134 , Senter L 120 , Sharma P 135 , Simard J 136 , Singer CF 125 , Sinilnikova OM 39 , Soucy P 136 , Southey M 137 , Steinemann D 138 , Stenmark-Askmalm M 139 , Stoppa-Lyonnet D 140 , Swerdlow A 90 , Szabo CI 141 , Tamimi R 52 , Tapper W 49 , Teixeira MR 142 , Teo SH 143 , Terry MB 144 , Thomassen M 145 , Thompson D 2 , Tihomirova L 146 , Toland AE 147 , Tollenaar RA 148 , Tomlinson I 149 , Truong T 72 , Tsimiklis H 137 , Teulé A 150 , Tumino R 151 , Tung N 152 , Turnbull C 123 , Ursin G 153 , van Deurzen CH 154 , van Rensburg EJ 45 , Varon-Mateeva R 155 , Wang Z 156 , Wang-Gohrke S 157 , Weiderpass E 37 , Weitzel JN 78 , Whittemore A 158 , Wildiers H 159 , Winqvist R 121 , Yang XR 160 , Yannoukakos D 55 , Yao S 9 , Zamora MP 161 , Zheng W 106 , Hall P 37 , Kraft P 104 , Vachon C 5 , Slager S 5 , Chenevix-Trench G 162 , Pharoah PD 48 , Monteiro AA 3 , García-Closas M 163 , Easton DF 2 , Antoniou AC 2

Affiliations 

  • 1 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
  • 2 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
  • 3 Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
  • 4 Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, N-0310 Oslo, Norway
  • 5 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA
  • 6 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV-IRCCS, 20133 Padua, Italy
  • 7 Department of Health Studies, The University of Chicago, Chicago, Illinois 60637, USA
  • 8 Department of Clinical Genetics, Helsinki University Central Hospital, 00029 Helsinki, Finland
  • 9 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
  • 10 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
  • 11 Department of Epidemiology, University of California Irvine, Irvine, California, 92697, USA
  • 12 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 13 University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
  • 14 Department of Oncology, Karolinska University Hospital, SE-17176 Stockholm, Sweden
  • 15 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, 20141 Milan, Italy
  • 16 Department of Pathology, Landspitali University Hospital and University of Iceland School of Medicine, 101 Reykjavik, Iceland
  • 17 Institute for Quality and Efficiency in Health Care (IQWiG), 50670 Cologne, Germany
  • 18 University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany
  • 19 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain
  • 20 NYU Women's Cancer Program, New York University School of Medicine, New York, New York 10016, USA
  • 21 Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland
  • 22 Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany
  • 23 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
  • 24 Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany
  • 25 Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, Germany
  • 26 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City Utah 84112, USA
  • 27 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid 28040, Spain
  • 28 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, I-56126 Pisa, Italy
  • 29 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 30 Australian Breast Cancer Tissue Bank, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia
  • 31 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 32 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20850, USA
  • 33 Departments of Pediatrics and Medicine, Columbia University, New York, New York 10032, USA
  • 34 Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium
  • 35 Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK
  • 36 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
  • 37 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden
  • 38 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
  • 39 INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France
  • 40 Department of Human Genetics and Department of Pathology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands
  • 41 Oncogenetics Group, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
  • 42 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA
  • 43 Cancer Bioimmunotherapy Unit, CRO Aviano National Cancer Institute, 33081 Aviano , Italy
  • 44 Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Pennsylvania 19104, USA
  • 45 Department of Genetics, University of Pretoria, Pretoria 0007, South Africa
  • 46 Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK
  • 47 Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada G1V 4G2
  • 48 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
  • 49 Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, Hampshire SO16 6YD, UK
  • 50 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala SE-751 85, Sweden
  • 51 Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany
  • 52 Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
  • 53 Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, 20246 Hamburg, Germany
  • 54 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 55 Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, 15310 Athens, Greece
  • 56 Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4
  • 57 University of, Philadelphia, Pennsylvania 19104, USA
  • 58 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel
  • 59 Department of Epidemiology, University of, Chapel Hill, North Carolina 27599-7400, USA
  • 60 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-6900, USA
  • 61 Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA
  • 62 Cancer Risk and Prevention Clinic, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA
  • 63 Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, California 90048, USA
  • 64 Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark
  • 65 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3010, Australia
  • 66 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, 66205, USA
  • 67 Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 2M1
  • 68 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
  • 69 Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
  • 70 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850-9772, USA
  • 71 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 72 Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, 70-115 Villejuif, France
  • 73 Department of of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK
  • 74 Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA
  • 75 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 76 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark
  • 77 Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia
  • 78 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California 91010, USA
  • 79 Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam 1000 BE, The Netherlands
  • 80 Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam 3008 AE, The Netherlands
  • 81 Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam 3008 AE, The Netherlands
  • 82 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia
  • 83 Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
  • 84 N.N. Petrov Institute of Oncology, 197758 St Petersburg, Russia
  • 85 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA
  • 86 Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia
  • 87 State Research Institute Centre for Innovative Medicine, LT-08661 Vilnius, Lithuania
  • 88 Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus N, Denmark
  • 89 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA
  • 90 Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton SM2 5NG, UK
  • 91 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA
  • 92 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland
  • 93 Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK
  • 94 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
  • 95 Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53113 Bonn, Germany
  • 96 School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland
  • 97 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong
  • 98 Vesalius Research Center, VIB, 3000 Leuven, Belgium
  • 99 Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, 08908 Barcelona, Spain
  • 100 Department of Preventive Medicine, University of Southern California, Los Angeles, California 90032, USA
  • 101 Cancer Epidemiology Program, University of Cancer Center, Honolulu, Hawaii 96813, USA
  • 102 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden
  • 103 Health Sciences Research, Mayo Clinic, Scotsdale, Arizona 85259, USA
  • 104 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
  • 105 Human Genetics Division, Genome Institute of Singapore, Singapore 138672, Singapore
  • 106 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA
  • 107 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
  • 108 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), 20133 Milan, Italy
  • 109 Department of Gynaecology and Obstetrics, Technical University of Munich, 81675 Munich, Germany
  • 110 NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
  • 111 Department of Genomics and Genome Sciences, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
  • 112 Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada M5B 1W8
  • 113 Invitae Corporation, San Francisco, California 94107, USA
  • 114 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA
  • 115 Department of Molecular Genetics, National Institute of Oncology, H-1122 Budapest, Hungary
  • 116 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA
  • 117 Department of Preventive Medicine and Biomedical Science, Seoul National University College of Medicine and Cancer Research Institute, Seoul National University, 110-799 Seoul, Republic of Korea
  • 118 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht 3508 GA, The Netherlands
  • 119 IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20133 Milan, Italy
  • 120 Divison of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA
  • 121 Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu/Oulu University Hospital, FI-90220 Oulu, Finland
  • 122 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), 20133 Milan, Italy
  • 123 Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK
  • 124 Department of Clinical Genetics, Karolinska University Hospital, SE-17176 Stockholm, Sweden
  • 125 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, A 1090 Vienna, Austria
  • 126 Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Haifa 34362, Israel
  • 127 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
  • 128 International Agency for Research on Cancer, 69008 Lyon, France
  • 129 Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam 1006 BE, The Netherlands
  • 130 Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18014 Granada, Spain
  • 131 Department of Environmental Health Sciences, Columbia University, New York, New York, 10032, USA
  • 132 Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London SE1 9RT, UK
  • 133 Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, University Hospital Cologne, Cologne 50931, Germany
  • 134 Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales 2305, Australia
  • 135 Department of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas 66205, USA
  • 136 Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec City, Quebec, Canada G1V 4G2
  • 137 Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
  • 138 Hannover Medical School, 30625 Hannover, Germany
  • 139 Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, SE-58185 Linköping, Sweden
  • 140 Institut Curie, Department of Tumour Biology, 75248 Paris, France
  • 141 National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-2152, USA
  • 142 Department of Genetics, Portuguese Oncology Institute, Porto, 4200-072, Portugal
  • 143 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya 47500, Malaysia
  • 144 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, 10032, USA
  • 145 Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark
  • 146 Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
  • 147 Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, 43210, USA
  • 148 Department of Surgical Oncology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands
  • 149 Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK
  • 150 Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, 08908 Barcelona, Spain
  • 151 Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, 97100 ASP Ragusa, Italy
  • 152 Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA
  • 153 Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway
  • 154 Department of Pathology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam 3000 CA, The Netherlands
  • 155 Institute of Human Genetics, Charite Berlin, 13353 Berlin, Germany
  • 156 Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA
  • 157 University Hospital Ulm, 89075 Ulm, , Germany
  • 158 Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California 94305, USA
  • 159 Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals, B-3000 Leuven, Belgium
  • 160 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA
  • 161 Servicio de Oncología Médica, Hospital Universitario La Paz, 28046 Madrid, Spain
  • 162 Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia
  • 163 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA
Nat Commun, 2016 04 27;7:11375.
PMID: 27117709 DOI: 10.1038/ncomms11375

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.