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 K^1,², Lindström S^3,⁴, 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 Z^9,¹⁰, 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 H^4,¹⁵, Adams M¹⁶, Adank MA¹⁷, Ahsan H¹⁸, Aittomäki K¹⁹, Anton-Culver H²⁰, Antonenkova NN²¹, Arndt V²², Aronson KJ²³, Arun B²⁴, Auer PL^25,²⁶, Bacot F²⁷, Barrdahl M¹², Baynes C⁷, Beckmann MW²⁸, Behrens S¹², Benitez J^29,³⁰, Bermisheva M³¹, Bernstein L³², Blomqvist C³³, Bogdanova NV^21,^34,³⁵, Bojesen SE^36,^37,³⁸, Bonanni B³⁹, Børresen-Dale AL⁴⁰, Brand JS⁴¹, Brauch H^42,^43,⁴⁴, Brennan P⁴⁵, Brenner H^22,^44,⁴⁶, Brinton L⁴⁷, Broberg P⁴⁸, Brock IW⁴⁹, Broeks A¹¹, Brooks-Wilson A^50,⁵¹, Brucker SY⁵², Brüning T⁵³, Burwinkel B^54,⁵⁵, Butterbach K²², Cai Q⁵⁶, Cai H⁵⁶, Caldés T⁵⁷, Canzian F⁵⁸, Carracedo A^59,⁶⁰, Carter BD⁶¹, Castelao JE⁶², Chan TL^63,⁶⁴, David Cheng TY⁶⁵, Seng Chia K⁶⁶, Choi JY^67,⁶⁸, Christiansen H³⁴, Clarke CL⁶⁹; NBCS Collaborators, Collée M⁷⁰, Conroy DM⁷, Cordina-Duverger E⁷¹, Cornelissen S¹¹, Cox DG^72,⁷³, Cox A⁴⁹, Cross SS⁷⁴, Cunningham JM⁷⁵, Czene K⁴¹, Daly MB⁷⁶, Devilee P^77,⁷⁸, Doheny KF¹⁶, Dörk T³⁵, Dos-Santos-Silva I⁷⁹, Dumont M⁸, Durcan L^80,⁸¹, Dwek M⁸², Eccles DM⁸¹, Ekici AB⁸³, Eliassen AH^84,⁸⁵, Ellberg C^48,⁸⁶, Elvira M⁸⁷, Engel C^88,⁸⁹, Eriksson M⁴¹, Fasching PA^28,⁹⁰, Figueroa J^47,⁹¹, Flesch-Janys D^92,⁹³, Fletcher O⁹⁴, Flyger H⁹⁵, Fritschi L⁹⁶, Gaborieau V⁴⁵, Gabrielson M⁴¹, Gago-Dominguez M^59,⁹⁷, Gao YT⁹⁸, Gapstur SM⁶¹, García-Sáenz JA⁵⁷, Gaudet MM⁶¹, Georgoulias V⁹⁹, Giles GG^100,¹⁰¹, Glendon G¹⁰², Goldberg MS^103,¹⁰⁴, Goldgar DE¹⁰⁵, González-Neira A²⁹, Grenaker Alnæs GI⁴⁰, Grip M¹⁰⁶, Gronwald J¹⁰⁷, Grundy A¹⁰⁸, Guénel P⁷¹, Haeberle L²⁸, Hahnen E^109,^110,¹¹¹, Haiman CA¹¹², Håkansson N¹¹³, Hamann U¹¹⁴, Hamel N²⁷, Hankinson S¹¹⁵, Harrington P⁷, Hart SN¹¹⁶, Hartikainen JM^117,^118,¹¹⁹, Hartman M^66,¹²⁰, 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 J^125,¹²⁶, Ito H^125,¹²⁶, Iwasaki M¹²⁷, Iwata H¹²⁸, Jakubowska A¹⁰⁷, Janni W¹²⁹, John EM^130,^131,¹³², Johnson N⁹⁴, Jones K¹⁰, Jones M¹³³, Jukkola-Vuorinen A¹³⁴, Kaaks R¹², Kabisch M¹¹⁴, Kaczmarek K¹⁰⁷, Kang D^67,^68,¹³⁵, Kasuga Y¹³⁶, Kerin MJ¹³⁷, Khan S¹³⁸, Khusnutdinova E^31,⁸⁷, Kiiski JI¹³⁸, Kim SW¹³⁹, Knight JA^140,¹⁴¹, Kosma VM^117,^118,¹¹⁹, Kristensen VN^40,^142,¹⁴³, Krüger U⁴⁸, Kwong A^63,^144,¹⁴⁵, Lambrechts D^146,¹⁴⁷, Le Marchand L¹⁴⁸, Lee E¹¹², Lee MH¹⁴⁹, Lee JW¹⁵⁰, Neng Lee C^120,¹⁵¹, Lejbkowicz F¹⁵², Li J⁴¹, Lilyquist J¹¹⁶, Lindblom A¹⁵³, Lissowska J¹⁵⁴, Lo WY^42,⁴³, Loibl S¹⁵⁵, Long J⁵⁶, Lophatananon A^156,¹⁵⁷, Lubinski J¹⁰⁷, Luccarini C⁷, Lux MP²⁸, Ma ESK^63,⁶⁴, MacInnis RJ^100,¹⁰¹, Maishman T^80,⁸¹, Makalic E¹⁰¹, Malone KE¹⁵⁸, Kostovska IM¹⁵⁹, Mannermaa A^117,^118,¹¹⁹, Manoukian S¹⁶⁰, Manson JE^85,¹⁶¹, Margolin S¹⁶², Mariapun S¹⁶³, Martinez ME^97,¹⁶⁴, Matsuo K^126,¹⁶⁵, Mavroudis D⁹⁹, McKay J⁴⁵, McLean C¹⁶⁶, Meijers-Heijboer H¹⁷, Meindl A¹⁶⁷, Menéndez P¹⁶⁸, Menon U¹⁶⁹, Meyer J⁷⁵, Miao H⁶⁶, Miller N¹³⁷, Taib NAM¹⁷⁰, Muir K^156,¹⁵⁷, Mulligan AM^171,¹⁷², Mulot C¹⁷³, Neuhausen SL³², Nevanlinna H¹³⁸, Neven P¹⁷⁴, Nielsen SF^36,³⁷, Noh DY¹⁷⁵, Nordestgaard BG^36,^37,³⁸, Norman A¹¹⁶, Olopade OI¹⁷⁶, Olson JE¹¹⁶, Olsson H⁴⁸, Olswold C¹¹⁶, Orr N⁹⁴, Pankratz VS¹⁷⁷, Park SK^67,^68,¹³⁵, Park-Simon TW³⁵, Lloyd R¹⁷⁸, Perez JIA¹⁷⁹, Peterlongo P¹⁸⁰, Peto J⁷⁹, Phillips KA^101,^181,^182,¹⁸³, Pinchev M¹⁵², Plaseska-Karanfilska D¹⁵⁹, Prentice R²⁵, Presneau N⁸², Prokofyeva D⁸⁷, Pugh E¹⁶, Pylkäs K^184,¹⁸⁵, Rack B¹⁸⁶, Radice P¹⁸⁷, Rahman N¹⁸⁸, Rennert G¹⁵², Rennert HS¹⁵², Rhenius V⁷, Romero A^57,¹⁸⁹, Romm J¹⁶, Ruddy KJ¹⁹⁰, Rüdiger T¹⁹¹, Rudolph A¹², Ruebner M²⁸, Rutgers EJT¹⁹², Saloustros E¹⁹³, Sandler DP¹⁹⁴, Sangrajrang S¹⁹⁵, Sawyer EJ¹⁹⁶, Schmidt DF¹⁰¹, Schmutzler RK^109,^110,¹¹¹, Schneeweiss A^54,¹⁹⁷, Schoemaker MJ¹³³, Schumacher F¹⁹⁸, Schürmann P³⁵, Scott RJ^199,²⁰⁰, Scott C¹¹⁶, Seal S¹⁸⁸, Seynaeve C¹²², Shah M⁷, Sharma P²⁰¹, Shen CY^202,²⁰³, Sheng G¹¹², Sherman ME²⁰⁴, Shrubsole MJ⁵⁶, Shu XO⁵⁶, Smeets A¹⁷⁴, Sohn C¹⁹⁷, Southey MC²⁰⁵, Spinelli JJ^206,²⁰⁷, Stegmaier C²⁰⁸, Stewart-Brown S¹⁵⁶, Stone J^178,²⁰⁹, Stram DO¹¹², Surowy H^54,⁵⁵, Swerdlow A^133,²¹⁰, Tamimi R^4,^84,⁸⁵, Taylor JA^194,²¹¹, Tengström M^117,^212,²¹³, Teo SH^163,¹⁷⁰, Beth Terry M²¹⁴, Tessier DC²⁷, Thanasitthichai S²¹⁵, Thöne K⁹³, Tollenaar RAEM²¹⁶, Tomlinson I²¹⁷, Tong L¹⁸, Torres D^114,²¹⁸, Truong T⁷¹, Tseng CC¹¹², Tsugane S²¹⁹, Ulmer HU²²⁰, Ursin G^221,²²², 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 AS^131,¹³², Wildiers H¹⁷⁴, Willett W^85,²²⁹, Winqvist R^184,¹⁸⁵, Wolk A¹¹³, Wu AH¹¹², Xia L¹¹², Yamaji T¹²⁷, Yang XR⁴⁷, Har Yip C²³⁰, Yoo KY^231,²³², Yu JC²³³, Zheng W⁵⁶, Zheng Y²³⁴, Zhu B¹⁰, Ziogas A²⁰, Ziv E²³⁵; ABCTB Investigators; ConFab/AOCS Investigators, Lakhani SR^13,²³⁶, Antoniou AC¹, Droit A⁸, Andrulis IL^102,²³⁷, Amos CI²³⁸, Couch FJ⁷⁵, Pharoah PDP^1,⁷, Chang-Claude J^12,²³⁹, Hall P^41,²⁴⁰, Hunter DJ^4,⁸⁵, Milne RL^100,¹⁰¹, García-Closas M⁴⁷, Schmidt MK^11,²⁴¹, Chanock SJ⁴⁷, Dunning AM⁷, Edwards SL⁵, Bader GD⁶, Chenevix-Trench G⁵, Simard J⁸, Kraft P^4,⁸⁵, Easton DF^1,⁷.

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.