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Nat Commun. 2016 Apr 27;7:11375. doi: 10.1038/ncomms11375.

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.

Couch FJ1,2, Kuchenbaecker KB3, Michailidou K3, Mendoza-Fandino GA4, Nord S5, Lilyquist J2, Olswold C2, Hallberg E2, Agata S6, Ahsan H7,8,9, Aittomäki K10, Ambrosone C11, Andrulis IL12,13, Anton-Culver H14, Arndt V15, Arun BK16, Arver B17, Barile M18, Barkardottir RB19, Barrowdale D3, Beckmann L20, Beckmann MW21, Benitez J22,23,24, Blank SV25, Blomqvist C26, Bogdanova NV27, Bojesen SE28, Bolla MK3, Bonanni B18, Brauch H29,30, Brenner H15,31, Burwinkel B32, Buys SS33, Caldes T34, Caligo MA35, Canzian F36, Carpenter J37, Chang-Claude J38, Chanock SJ39, Chung WK40, Claes KB41, Cox A42, Cross SS43, Cunningham JM1, Czene K44, Daly MB45, Damiola F46, Darabi H44, de la Hoya M34, Devilee P47, Diez O48, Ding YC49, Dolcetti R50, Domchek SM51, Dorfling CM52, Dos-Santos-Silva I53, Dumont M54, Dunning AM55, Eccles DM56, Ehrencrona H57,58, Ekici AB59,60, Eliassen H61,62, Ellis S3, Fasching PA21, Figueroa J39, Flesch-Janys D63, Försti A64,65, Fostira F66, Foulkes WD67, Friebel T68, Friedman E69, Frost D3, Gabrielson M44, Gammon MD70, Ganz PA71, Gapstur SM72, Garber J73, Gaudet MM72, Gayther SA74, Gerdes AM75, Ghoussaini M55, Giles GG76, Glendon G12, Godwin AK77, Goldberg MS78,79, Goldgar DE80, González-Neira A81, Greene MH82, Gronwald J83, Guénel P84, Gunter M85, Haeberle L21, Haiman CA86, Hamann U87, Hansen TV88, Hart S2, Healey S89, Heikkinen T32,90, Henderson BE86, Herzog J91, Hogervorst FB92, Hollestelle A93, Hooning MJ94, Hoover RN39, Hopper JL95, Humphreys K44, Hunter DJ96, Huzarski T83, Imyanitov EN97, Isaacs C98, Jakubowska A83, James P99,100, Janavicius R101, Jensen UB102, John EM103, Jones M104, Kabisch M87, Kar S55, Karlan BY105, Khan S106, Khaw KT107, Kibriya MG7, Knight JA108, Ko YD109, Konstantopoulou I66, Kosma VM110, Kristensen V5, Kwong A111,112, Laitman Y69, Lambrechts D113, Lazaro C114, Lee E115, Le Marchand L116, Lester J105, Lindblom A117, Lindor N118, Lindstrom S62,119, Liu J120, Long J121, Lubinski J83, Mai PL82, Makalic E95, Malone KE122,123, Mannermaa A110, Manoukian S124, Margolin S17, Marme F32, Martens JW93, McGuffog L3, Meindl A125, Miller A126, Milne RL76, Miron P127, Montagna M6, Mazoyer S46, Mulligan AM128,129, Muranen TA32,90, Nathanson KL51, Neuhausen SL49, Nevanlinna H106, Nordestgaard BG28, Nussbaum RL130, Offit K131, Olah E132, Olopade OI133, Olson JE2, Osorio A22, Park SK134, Peeters PH135,136, Peissel B124, Peterlongo P137, Peto J53, Phelan CM4, Pilarski R138, Poppe B41, Pylkäs K139, Radice P140, Rahman N141, Rantala J142, Rappaport C143, Rennert G144, Richardson A145, Robson M131, Romieu I146, Rudolph A38, Rutgers EJ147, Sanchez MJ148,149, Santella RM150, Sawyer EJ151, Schmidt DF95, Schmidt MK147, Schmutzler RK152,153,154, Schumacher F86, Scott R155, Senter L138, Sharma P156, Simard J157, Singer CF143, Sinilnikova OM46,158, Soucy P157, Southey M159, Steinemann D160, Stenmark-Askmalm M161, Stoppa-Lyonnet D162,163, Swerdlow A104, Szabo CI164, Tamimi R61,62,119, Tapper W56, Teixeira MR165,166, Teo SH167,168, Terry MB169, Thomassen M170, Thompson D3, Tihomirova L171, Toland AE172, Tollenaar RA173, Tomlinson I174, Truong T84, Tsimiklis H159, Teulé A175, Tumino R176, Tung N177, Turnbull C141, Ursin G178, van Deurzen CH179, van Rensburg EJ52, Varon-Mateeva R180, Wang Z181, Wang-Gohrke S182, Weiderpass E44,178,183,184, Weitzel JN91, Whittemore A185, Wildiers H186, Winqvist R139, Yang XR187, Yannoukakos D66, Yao S11, Zamora MP188, Zheng W121, Hall P44, Kraft P62,119,189, Vachon C2, Slager S2, Chenevix-Trench G190, Pharoah PD55, Monteiro AA4, García-Closas M191, Easton DF3, Antoniou AC3.

Author information

1
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
2
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
3
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
4
Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
5
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, N-0310 Oslo, Norway.
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
Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois 60637, USA.
9
Departments of Medicine and Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA.
10
Department of Clinical Genetics, Helsinki University Central Hospital, 00029 Helsinki, Finland.
11
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
12
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
13
Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada M5B 1W8.
14
Department of Epidemiology, University of California Irvine, Irvine, California, 92697, USA.
15
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
16
University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
17
Department of Oncology, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
18
Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, 20141 Milan, Italy.
19
Department of Pathology, Landspitali University Hospital and University of Iceland School of Medicine, 101 Reykjavik, Iceland.
20
Institute for Quality and Efficiency in Health Care (IQWiG), 50670 Cologne, Germany.
21
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.
22
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain.
23
Genotyping Unit (CeGen), Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain.
24
Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain.
25
NYU Women's Cancer Program, New York University School of Medicine, New York, New York 10016, USA.
26
Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
27
Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany.
28
Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.
29
Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.
30
University of Tübingen 72074 Tübingen, Germany.
31
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.
32
Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, Germany.
33
Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City Utah 84112, USA.
34
Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid 28040, Spain.
35
Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, I-56126 Pisa, Italy.
36
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
37
Australian Breast Cancer Tissue Bank, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia.
38
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
39
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20850, USA.
40
Departments of Pediatrics and Medicine, Columbia University, New York, New York 10032, USA.
41
Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
42
Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK.
43
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
44
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
45
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
46
INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France.
47
Department of Human Genetics and Department of Pathology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
48
Oncogenetics Group, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
49
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
50
Cancer Bioimmunotherapy Unit, CRO Aviano National Cancer Institute, 33081 Aviano , Italy.
51
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Pennsylvania 19104, USA.
52
Department of Genetics, University of Pretoria, Pretoria 0007, South Africa.
53
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
54
Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada G1V 4G2.
55
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
56
Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, Hampshire SO16 6YD, UK.
57
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala SE-751 85, Sweden.
58
Department of Clinical Genetics, Lund University Hospital, SE-22185 Lund, Sweden.
59
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
60
Comprehensive Cancer Center -EMN, 91054 Erlangen, Germany.
61
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
62
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
63
Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, 20246 Hamburg, Germany.
64
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
65
Center for Primary Health Care Research, Lund University, SE-221 00 Malmö, Sweden.
66
Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, 15310 Athens, Greece.
67
Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4.
68
University of, Philadelphia, Pennsylvania 19104, USA.
69
Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel.
70
Department of Epidemiology, University of, Chapel Hill, North Carolina 27599-7400, USA.
71
UCLA Schools of Medicine and Public Health, Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-6900, USA.
72
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
73
Cancer Risk and Prevention Clinic, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA.
74
Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
75
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
76
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3010, Australia.
77
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, 66205, USA.
78
Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 2M1.
79
Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada H4A 3J1.
80
Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
81
Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
82
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850-9772, USA.
83
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
84
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.
85
Department of of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK.
86
Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
87
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
88
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
89
Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
90
Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
91
Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California 91010, USA.
92
Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam 1000 BE, The Netherlands.
93
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam 3008 AE, The Netherlands.
94
Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam 3008 AE, The Netherlands.
95
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
96
Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
97
N.N. Petrov Institute of Oncology, 197758 St Petersburg, Russia.
98
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
99
Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia.
100
Department of Oncology, The University of Melbourne, Melbourne, Victoria 8006, Australia.
101
State Research Institute Centre for Innovative Medicine, LT-08661 Vilnius, Lithuania.
102
Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus N, Denmark.
103
Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA.
104
Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton SM2 5NG, UK.
105
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
106
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
107
Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
108
Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
109
Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53113 Bonn, Germany.
110
School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
111
The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong.
112
Department of Surgery, The University of Hong Kong, Hong Kong, China.
113
Vesalius Research Center, VIB, 3000 Leuven, Belgium.
114
Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, 08908 Barcelona, Spain.
115
Department of Preventive Medicine, University of Southern California, Los Angeles, California 90032, USA.
116
Cancer Epidemiology Program, University of Cancer Center, Honolulu, Hawaii 96813, USA.
117
Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden.
118
Health Sciences Research, Mayo Clinic, Scotsdale, Arizona 85259, USA.
119
Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
120
Human Genetics Division, Genome Institute of Singapore, Singapore 138672, Singapore.
121
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
122
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
123
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98195, USA.
124
Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), 20133 Milan, Italy.
125
Department of Gynaecology and Obstetrics, Technical University of Munich, 81675 Munich, Germany.
126
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
127
Department of Genomics and Genome Sciences, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA.
128
Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada M5B 1W8.
129
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5B 1W8.
130
Invitae Corporation, San Francisco, California 94107, USA.
131
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
132
Department of Molecular Genetics, National Institute of Oncology, H-1122 Budapest, Hungary.
133
Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
134
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.
135
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht 3508 GA, The Netherlands.
136
MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK.
137
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20133 Milan, Italy.
138
Divison of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
139
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.
140
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.
141
Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK.
142
Department of Clinical Genetics, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
143
Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, A 1090 Vienna, Austria.
144
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.
145
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
146
International Agency for Research on Cancer, 69008 Lyon, France.
147
Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam 1006 BE, The Netherlands.
148
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18014 Granada, Spain.
149
CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
150
Department of Environmental Health Sciences, Columbia University, New York, New York, 10032, USA.
151
Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London SE1 9RT, UK.
152
Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, University Hospital Cologne, Cologne 50931, Germany.
153
Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, 50931 Cologne, Germany.
154
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
155
Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales 2305, Australia.
156
Department of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas 66205, USA.
157
Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec City, Quebec, Canada G1V 4G2.
158
Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon-Centre Léon Bérard, 69373 Lyon, France.
159
Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
160
Hannover Medical School, 30625 Hannover, Germany.
161
Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, SE-58185 Linköping, Sweden.
162
Institut Curie, Department of Tumour Biology, 75248 Paris, France.
163
Université Paris Descartes, Sorbonne Paris Cité, 75248 Paris, France.
164
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-2152, USA.
165
Department of Genetics, Portuguese Oncology Institute, Porto, 4200-072, Portugal.
166
Biomedical Sciences Institute (ICBAS), Porto University, 4200-072 Porto, Portugal.
167
Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya 47500, Malaysia.
168
University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, Kuala Lumpur 50603, Malaysia.
169
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, 10032, USA.
170
Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark.
171
Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia.
172
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, 43210, USA.
173
Department of Surgical Oncology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
174
Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK.
175
Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, 08908 Barcelona, Spain.
176
Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, 97100 ASP Ragusa, Italy.
177
Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA.
178
Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway.
179
Department of Pathology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam 3000 CA, The Netherlands.
180
Institute of Human Genetics, Charite Berlin, 13353 Berlin, Germany.
181
Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA.
182
University Hospital Ulm, 89075 Ulm, , Germany.
183
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
184
Genetic Epidemiology Group, Folkhälsan Research Center, 2016 Helsinki, Finland.
185
Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California 94305, USA.
186
Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals, B-3000 Leuven, Belgium.
187
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
188
Servicio de Oncología Médica, Hospital Universitario La Paz, 28046 Madrid, Spain.
189
Department of Biostatistics, Harvard School Of Public Health, Boston, Massachusetts 02115, USA.
190
Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
191
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA.

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.

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