Format

Send to

Choose Destination
Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.

Association analysis identifies 65 new breast cancer risk loci.

Michailidou K1,2, Lindström S3,4, Dennis J1, Beesley J5, Hui S6, Kar S7, Lemaçon A8, Soucy P8, Glubb D5, Rostamianfar A6, Bolla MK1, Wang Q1, Tyrer J7, Dicks E7, Lee A1, Wang Z9,10, Allen J1, Keeman R11, Eilber U12, French JD5, Qing Chen X5, Fachal L7, McCue K5, McCart Reed AE13, Ghoussaini M7, Carroll JS14, Jiang X4, Finucane H4,15, Adams M16, Adank MA17, Ahsan H18, Aittomäki K19, Anton-Culver H20, Antonenkova NN21, Arndt V22, Aronson KJ23, Arun B24, Auer PL25,26, Bacot F27, Barrdahl M12, Baynes C7, Beckmann MW28, Behrens S12, Benitez J29,30, Bermisheva M31, Bernstein L32, Blomqvist C33, Bogdanova NV21,34,35, Bojesen SE36,37,38, Bonanni B39, Børresen-Dale AL40, Brand JS41, Brauch H42,43,44, Brennan P45, Brenner H22,44,46, Brinton L47, Broberg P48, Brock IW49, Broeks A11, Brooks-Wilson A50,51, Brucker SY52, Brüning T53, Burwinkel B54,55, Butterbach K22, Cai Q56, Cai H56, Caldés T57, Canzian F58, Carracedo A59,60, Carter BD61, Castelao JE62, Chan TL63,64, David Cheng TY65, Seng Chia K66, Choi JY67,68, Christiansen H34, Clarke CL69; NBCS Collaborators, Collée M70, Conroy DM7, Cordina-Duverger E71, Cornelissen S11, Cox DG72,73, Cox A49, Cross SS74, Cunningham JM75, Czene K41, Daly MB76, Devilee P77,78, Doheny KF16, Dörk T35, Dos-Santos-Silva I79, Dumont M8, Durcan L80,81, Dwek M82, Eccles DM81, Ekici AB83, Eliassen AH84,85, Ellberg C48,86, Elvira M87, Engel C88,89, Eriksson M41, Fasching PA28,90, Figueroa J47,91, Flesch-Janys D92,93, Fletcher O94, Flyger H95, Fritschi L96, Gaborieau V45, Gabrielson M41, Gago-Dominguez M59,97, Gao YT98, Gapstur SM61, García-Sáenz JA57, Gaudet MM61, Georgoulias V99, Giles GG100,101, Glendon G102, Goldberg MS103,104, Goldgar DE105, González-Neira A29, Grenaker Alnæs GI40, Grip M106, Gronwald J107, Grundy A108, Guénel P71, Haeberle L28, Hahnen E109,110,111, Haiman CA112, Håkansson N113, Hamann U114, Hamel N27, Hankinson S115, Harrington P7, Hart SN116, Hartikainen JM117,118,119, Hartman M66,120, Hein A28, Heyworth J121, Hicks B10, Hillemanns P35, Ho DN64, Hollestelle A122, Hooning MJ122, Hoover RN47, Hopper JL101, Hou MF123, Hsiung CN124, Huang G114, Humphreys K41, Ishiguro J125,126, Ito H125,126, Iwasaki M127, Iwata H128, Jakubowska A107, Janni W129, John EM130,131,132, Johnson N94, Jones K10, Jones M133, Jukkola-Vuorinen A134, Kaaks R12, Kabisch M114, Kaczmarek K107, Kang D67,68,135, Kasuga Y136, Kerin MJ137, Khan S138, Khusnutdinova E31,87, Kiiski JI138, Kim SW139, Knight JA140,141, Kosma VM117,118,119, Kristensen VN40,142,143, Krüger U48, Kwong A63,144,145, Lambrechts D146,147, Le Marchand L148, Lee E112, Lee MH149, Lee JW150, Neng Lee C120,151, Lejbkowicz F152, Li J41, Lilyquist J116, Lindblom A153, Lissowska J154, Lo WY42,43, Loibl S155, Long J56, Lophatananon A156,157, Lubinski J107, Luccarini C7, Lux MP28, Ma ESK63,64, MacInnis RJ100,101, Maishman T80,81, Makalic E101, Malone KE158, Kostovska IM159, Mannermaa A117,118,119, Manoukian S160, Manson JE85,161, Margolin S162, Mariapun S163, Martinez ME97,164, Matsuo K126,165, Mavroudis D99, McKay J45, McLean C166, Meijers-Heijboer H17, Meindl A167, Menéndez P168, Menon U169, Meyer J75, Miao H66, Miller N137, Taib NAM170, Muir K156,157, Mulligan AM171,172, Mulot C173, Neuhausen SL32, Nevanlinna H138, Neven P174, Nielsen SF36,37, Noh DY175, Nordestgaard BG36,37,38, Norman A116, Olopade OI176, Olson JE116, Olsson H48, Olswold C116, Orr N94, Pankratz VS177, Park SK67,68,135, Park-Simon TW35, Lloyd R178, Perez JIA179, Peterlongo P180, Peto J79, Phillips KA101,181,182,183, Pinchev M152, Plaseska-Karanfilska D159, Prentice R25, Presneau N82, Prokofyeva D87, Pugh E16, Pylkäs K184,185, Rack B186, Radice P187, Rahman N188, Rennert G152, Rennert HS152, Rhenius V7, Romero A57,189, Romm J16, Ruddy KJ190, Rüdiger T191, Rudolph A12, Ruebner M28, Rutgers EJT192, Saloustros E193, Sandler DP194, Sangrajrang S195, Sawyer EJ196, Schmidt DF101, Schmutzler RK109,110,111, Schneeweiss A54,197, Schoemaker MJ133, Schumacher F198, Schürmann P35, Scott RJ199,200, Scott C116, Seal S188, Seynaeve C122, Shah M7, Sharma P201, Shen CY202,203, Sheng G112, Sherman ME204, Shrubsole MJ56, Shu XO56, Smeets A174, Sohn C197, Southey MC205, Spinelli JJ206,207, Stegmaier C208, Stewart-Brown S156, Stone J178,209, Stram DO112, Surowy H54,55, Swerdlow A133,210, Tamimi R4,84,85, Taylor JA194,211, Tengström M117,212,213, Teo SH163,170, Beth Terry M214, Tessier DC27, Thanasitthichai S215, Thöne K93, Tollenaar RAEM216, Tomlinson I217, Tong L18, Torres D114,218, Truong T71, Tseng CC112, Tsugane S219, Ulmer HU220, Ursin G221,222, Untch M223, Vachon C116, van Asperen CJ224, Van Den Berg D112, van den Ouweland AMW70, van der Kolk L225, van der Luijt RB226, Vincent D27, Vollenweider J75, Waisfisz Q17, Wang-Gohrke S227, Weinberg CR228, Wendt C162, Whittemore AS131,132, Wildiers H174, Willett W85,229, Winqvist R184,185, Wolk A113, Wu AH112, Xia L112, Yamaji T127, Yang XR47, Har Yip C230, Yoo KY231,232, Yu JC233, Zheng W56, Zheng Y234, Zhu B10, Ziogas A20, Ziv E235; ABCTB Investigators; ConFab/AOCS Investigators, Lakhani SR13,236, Antoniou AC1, Droit A8, Andrulis IL102,237, Amos CI238, Couch FJ75, Pharoah PDP1,7, Chang-Claude J12,239, Hall P41,240, Hunter DJ4,85, Milne RL100,101, García-Closas M47, Schmidt MK11,241, Chanock SJ47, Dunning AM7, Edwards SL5, Bader GD6, Chenevix-Trench G5, Simard J8, Kraft P4,85, Easton DF1,7.

Author information

1
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
2
Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
3
Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA.
4
Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
5
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
6
The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
7
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
8
Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Quebec, Canada.
9
Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
10
Cancer Genomics Research Laboratory (CGR), Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
11
Division of Molecular Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
12
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
13
UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
14
Cancer Research UK Cambridge Research Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
15
Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
16
Center for Inherited Disease Research (CIDR), Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
17
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
18
Center for Cancer Epidemiology and Prevention, The University of Chicago, Chicago, Illinois, USA.
19
Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
20
Department of Epidemiology, University of California Irvine, Irvine, California, USA.
21
N. N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
22
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
23
Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
24
Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
25
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
26
Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
27
McGill University and Génome Québec Innovation Centre, Montréal, Quebec, Canada.
28
Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
29
Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.
30
Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
31
Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia.
32
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, USA.
33
Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
34
Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
35
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
36
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
37
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
38
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
39
Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.
40
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
41
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
42
Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
43
University of Tübingen, Tübingen, Germany.
44
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
45
International Agency for Research on Cancer, Lyon, France.
46
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
47
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
48
Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
49
Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
50
Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
51
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
52
Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany.
53
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany.
54
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
55
Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.
56
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
57
Medical Oncology Department, Hospital Clínico San Carlos, IdISSC (Centro Investigacion Biomedica en Red), CIBERONC (Instituto de Investigación Sanitaria San Carlos), Madrid, Spain.
58
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
59
Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago De Compostela, Spain.
60
Centro de Investigación en Red de Enfermedades Raras (CIBERER) y Centro Nacional de Genotipado (CEGEN-PRB2), Universidad de Santiago de Compostela, Santiago De Compostela, Spain.
61
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
62
Oncology and Genetics Unit, Instituto de Investigacion Biomedica (IBI) Orense-Pontevedra-Vigo, Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
63
Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong.
64
Department of Pathology, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong.
65
Division of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.
66
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
67
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea.
68
Cancer Research Institute, Seoul National University, Seoul, South Korea.
69
Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.
70
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
71
Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
72
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
73
INSERM U1052, Cancer Research Center of Lyon, Lyon, France.
74
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
75
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
76
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
77
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
78
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
79
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
80
Southampton Clinical Trials Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
81
Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
82
Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.
83
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
84
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
85
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
86
Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
87
Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia.
88
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
89
LIFE-Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
90
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, California, USA.
91
Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK.
92
Institute for Medical Biometrics and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
93
Department of Cancer Epidemiology, Clinical Cancer Registry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
94
Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
95
Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
96
School of Public Health, Curtin University, Perth, Australia.
97
Moores Cancer Center, University of California San Diego, La Jolla, California, USA.
98
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
99
Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
100
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
101
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
102
Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
103
Department of Medicine, McGill University, Montréal, Quebec, Canada.
104
Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montréal, Quebec, Canada.
105
Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
106
Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
107
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
108
Centre de Recherche du Centre Hospitalier de Université de Montréal (CHUM), Université de Montréal, Montréal, Quebec, Canada.
109
Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
110
Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany.
111
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
112
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
113
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
114
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
115
Department of Biostatistics & Epidemiology, University of Massachusetts, Amherst, Amherst, Massachusetts, USA.
116
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
117
Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
118
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
119
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
120
Department of Surgery, National University Health System, Singapore, Singapore.
121
School of Population Health, University of Western Australia, Perth, Australia.
122
Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
123
Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
124
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
125
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
126
Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
127
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
128
Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
129
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
130
Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California, USA.
131
Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California, USA.
132
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.
133
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
134
Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.
135
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
136
Department of Surgery, Nagano Matsushiro General Hospital, Nagano, Japan.
137
School of Medicine, National University of Ireland, Galway, Ireland.
138
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
139
Department of Surgery, Daerim Saint Mary's Hospital, Seoul, South Korea.
140
Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
141
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
142
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
143
Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway.
144
Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong.
145
Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong.
146
Vesalius Research Center, VIB, Leuven, Belgium.
147
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
148
University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
149
Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital, Seoul, South Korea.
150
Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
151
Department of Cardiac, Thoracic and Vascular Surgery, National University Health System, Singapore, Singapore.
152
Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
153
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
154
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland.
155
German Breast Group GmbH, Neu Isenburg, Germany.
156
Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
157
Institute of Population Health, University of Manchester, Manchester, UK.
158
Division of Public Health Sciences, Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
159
Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
160
Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy.
161
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
162
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
163
Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
164
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA.
165
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
166
Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
167
Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.
168
Servicio de Anatomía Patológica, Hospital Monte Naranco, Oviedo, Spain.
169
Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, University College London, London, UK.
170
Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
171
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
172
Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
173
Université Paris Sorbonne Cité, INSERM UMR-S1147, Paris, France.
174
Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
175
Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
176
Center for Clinical Cancer Genetics and Global Health, The University of Chicago, Chicago, Illinois, USA.
177
University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, New Mexico, USA.
178
The Curtin UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, Australia.
179
Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
180
IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.
181
Peter MacCallum Cancer Center, Melbourne, Australia.
182
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
183
Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Australia.
184
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.
185
Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland.
186
Department of Gynecology and Obstetrics, Ludwig-Maximilians University of Munich, Munich, Germany.
187
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy.
188
Section of Cancer Genetics, The Institute of Cancer Research, London, UK.
189
Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
190
Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
191
Institute of Pathology, Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany.
192
Department of Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
193
Hereditary Cancer Clinic, University Hospital of Heraklion, Heraklion, Greece.
194
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
195
National Cancer Institute, Bangkok, Thailand.
196
Research Oncology, Guy's Hospital, King's College London, London, UK.
197
National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
198
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
199
Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, Australia.
200
Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia.
201
Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
202
School of Public Health, China Medical University, Taichung, Taiwan.
203
Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
204
Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland, USA.
205
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
206
Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada.
207
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
208
Saarland Cancer Registry, Saarbrücken, Germany.
209
Department of Obstetrics and Gynaecology, University of Melbourne and the Royal Women's Hospital, Melbourne, Australia.
210
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
211
Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
212
Cancer Center, Kuopio University Hospital, Kuopio, Finland.
213
Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland.
214
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
215
National Cancer Institute, Ministry of Public Health, Nonthaburi, Thailand.
216
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
217
Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
218
Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
219
Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
220
Frauenklinik der Stadtklinik Baden-Baden, Baden-Baden, Germany.
221
Cancer Registry of Norway, Oslo, Norway.
222
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
223
Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany.
224
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
225
Family Cancer Clinic, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
226
Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
227
Department of Gynaecology and Obstetrics, University of Ulm, Ulm, Germany.
228
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
229
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
230
Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.
231
Seoul National University College of Medicine, Seoul, South Korea.
232
Armed Forces Capital Hospital, Seongnam, South Korea.
233
Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
234
Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
235
Department of Medicine, Institute for Human Genetics, UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
236
Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
237
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
238
Center for Genomic Medicine, Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA.
239
University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
240
Department of Oncology, Södersjukhuset, Stockholm, Sweden.
241
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

PMID:
29059683
PMCID:
PMC5798588
DOI:
10.1038/nature24284
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substance, Grant support

Publication types

MeSH terms

Substance

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central Icon for Norwegian BIBSYS system
Loading ...
Support Center