Article open access publication

Association analysis identifies 65 new breast cancer risk loci

Nature, Springer Nature, ISSN 1476-4687

Volume 551, 7678, 2017

DOI:10.1038/nature24284, Dimensions: pub.1092349555, PMC: PMC5798588, PMID: 29059683,

Authors

Wang, Qin (2)
Dicks, Ed (2)
Wang, Zhaoming (8) (9)
Finucane, Hilary (4) (14)
Arun, Banu (22)
Auer, Paul L. (23) (24)
Benitez, Javier (27) (28)
Bojesen, Stig E. (33) (34) (35)
Brauch, Hiltrud (11) (39) (40)
Burwinkel, Barbara (11) (47)
Cai, Hui (48)
Carracedo, Angel (50) (51)
Chan, Tsun L. (54) (55)
Cox, David G (62) (63)
Fasching, Peter A. (26) (74)
Figueroa, Jonine (9) (75)
Giles, Graham G (83) (84)
Hahnen, Eric (91) (92)
Hartman, Mikael (57) (97)
Ho, Dona N (54)
Ishiguro, Junko (101) (102)
Ito, Hidemi (101) (102)
John, Esther M (105) (106)
Khan, Sofia (110)
Knight, Julia A. (6) (85)
Kosma, Veli-Matti (95) (96)
Kristensen, Vessela N. (37) (112) (113)
Kwong, Ava (55) (114) (115)
Lambrechts, Diether (116) (117)
Lo, Wing-Yee (39) (40)
Ma, Edmond S K (54) (55)
Mannermaa, Arto (95) (96)
Manson, JoAnn E. (4) (128)
Matsuo, Keitaro (101) (102)
Menon, Usha (133)
Miao, Hui (57)
Muir, Kenneth (124) (125)
Nielsen, Sune F. (33) (34)
Nordestgaard, Børge G. (33) (34) (35)
Orr, Nick (77)
Phillips, Kelly-Anne (83) (141) (142)
Pylkäs, Katri (143) (144)
Romero, Atocha (49) (146)
Romm, Jane (15)
Scott, Rodney J (153) (154)
Shen, Chen-Yang (100) (156)
Smeets, Ann (137)
Spinelli, John J. (45) (157)
Stone, Jennifer (98) (159)
Surowy, Harald (11) (47)
Tamimi, Rulla (4) (71)
Taylor, Jack A (148) (160)
Tengström, Maria (95) (96)
Teo, Soo H. (129) (134)
Tong, Ling (17)
Torres, Diana (11) (164)
Ursin, Giske (113) (166)
Winqvist, Robert (143) (144)
Wu, Anna H (93)
Xia, Lucy (93)
Yoo, Keun-Young (58) (172)
Zheng, Wei (48)
Zheng, Ying (174)
Zhu, Bin (9)
Ziv, Elad (175)
Lakhani, Sunil R (12) (176)
Chang-Claude, Jenny (11) (178)
Hall, Per (38) (179)
Milne, Roger L. (83) (84)

* Corresponding author

Affiliations

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  1. (1) Cyprus Institute of Neurology and Genetics, grid.417705.0
  2. (2) University of Cambridge, grid.5335.0
  3. (3) University of Washington, grid.34477.33
  4. (4) Harvard University, grid.38142.3c
  5. (5) QIMR Berghofer Medical Research Institute, grid.1049.c
  6. (6) University of Toronto, grid.17063.33
  7. (7) Laval University, grid.23856.3a
  8. (8) St. Jude Children's Research Hospital, grid.240871.8
  9. (9) National Cancer Institute, grid.48336.3a
  10. (10) Antoni van Leeuwenhoek Hospital, grid.430814.a
  11. (11) German Cancer Research Center, grid.7497.d
  12. (12) University of Queensland, grid.1003.2
  13. (13) Cancer Research UK Cambridge Institute, grid.470869.4
  14. (14) Massachusetts Institute of Technology, grid.116068.8
  15. (15) Johns Hopkins University, grid.21107.35
  16. (16) VU University Medical Center, grid.16872.3a
  17. (17) Center for Cancer Epidemiology and Prevention, The University of Chicago, Chicago, Illinois, USA
  18. (18) Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  19. (19) University of California, Irvine, grid.266093.8
  20. (20) N. N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
  21. (21) Queen's University, grid.410356.5
  22. (22) The University of Texas MD Anderson Cancer Center, grid.240145.6
  23. (23) University of Wisconsin–Milwaukee, grid.267468.9
  24. (24) Fred Hutchinson Cancer Research Center, grid.270240.3
  25. (25) McGill University and Génome Québec Innovation Centre, grid.411640.6
  26. (26) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  27. (27) Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
  28. (28) Spanish National Cancer Research Centre, grid.7719.8
  29. (29) Institute of Biochemistry and Genetics of Ufa Scientific Centre, grid.429129.5
  30. (30) City Of Hope National Medical Center, grid.410425.6
  31. (31) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  32. (32) Hannover Medical School, grid.10423.34
  33. (33) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  34. (34) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  35. (35) University of Copenhagen, grid.5254.6, KU
  36. (36) European Institute of Oncology, grid.15667.33
  37. (37) Oslo University Hospital, grid.55325.34
  38. (38) Karolinska Institute, grid.4714.6
  39. (39) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  40. (40) University of Tübingen, grid.10392.39
  41. (41) International Agency For Research On Cancer, grid.17703.32
  42. (42) Lund University, grid.4514.4
  43. (43) University of Sheffield, grid.11835.3e
  44. (44) Simon Fraser University, grid.61971.38
  45. (45) BC Cancer Agency, grid.248762.d
  46. (46) Ruhr University Bochum, grid.5570.7
  47. (47) Heidelberg University, grid.7700.0
  48. (48) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  49. (49) Hospital Clínico San Carlos, grid.411068.a
  50. (50) University of Santiago de Compostela, grid.11794.3a
  51. (51) Complejo Hospitalario Universitario de Santiago, grid.411048.8
  52. (52) American Cancer Society, grid.422418.9
  53. (53) Oncology and Genetics Unit, Instituto de Investigacion Biomedica (IBI) Orense-Pontevedra-Vigo, Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain
  54. (54) Department of Pathology, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong
  55. (55) Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong
  56. (56) Roswell Park Cancer Institute, grid.240614.5
  57. (57) National University of Singapore, grid.4280.e
  58. (58) Seoul National University, grid.31501.36
  59. (59) University of Sydney, grid.1013.3
  60. (60) Erasmus University Medical Center, grid.5645.2
  61. (61) Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  62. (62) Cancer Center of Lyon, grid.462282.8
  63. (63) Imperial College London, grid.7445.2
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  69. (69) University of Westminster, grid.12896.34
  70. (70) Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  71. (71) Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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  73. (73) Leipzig University, grid.9647.c
  74. (74) University of California, Los Angeles, grid.19006.3e
  75. (75) University of Edinburgh, grid.4305.2
  76. (76) University Medical Center Hamburg-Eppendorf, grid.13648.38
  77. (77) Institute of Cancer Research, grid.18886.3f
  78. (78) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  79. (79) Curtin University, grid.1032.0
  80. (80) University of California, San Diego, grid.266100.3
  81. (81) Shanghai Cancer Institute, grid.419087.3
  82. (82) University Hospital of Heraklion, grid.412481.a
  83. (83) University of Melbourne, grid.1008.9
  84. (84) Cancer Council Victoria, grid.3263.4
  85. (85) Mount Sinai Hospital, grid.416166.2
  86. (86) McGill University, grid.14709.3b
  87. (87) University of Utah, grid.223827.e
  88. (88) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  89. (89) Pomeranian Medical University, grid.107950.a
  90. (90) University of Montreal, grid.14848.31
  91. (91) University Hospital Cologne, grid.411097.a
  92. (92) University of Cologne, grid.6190.e
  93. (93) University of Southern California, grid.42505.36
  94. (94) University of Massachusetts Amherst, grid.266683.f
  95. (95) Kuopio University Hospital, grid.410705.7
  96. (96) University of Eastern Finland, grid.9668.1
  97. (97) National University Health System, grid.410759.e
  98. (98) University of Western Australia, grid.1012.2
  99. (99) Kaohsiung Medical University, grid.412019.f
  100. (100) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  101. (101) Aichi Cancer Center, grid.410800.d
  102. (102) Nagoya University, grid.27476.30
  103. (103) National Cancer Centre, grid.272242.3
  104. (104) University Hospital Ulm, grid.410712.1
  105. (105) Cancer Prevention Institute of California, grid.280669.3
  106. (106) Stanford University, grid.168010.e
  107. (107) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
  108. (108) Nagano Matsushiro General Hospital, grid.452634.2
  109. (109) National University of Ireland, Galway, grid.6142.1
  110. (110) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  111. (111) Department of Surgery, Daerim Saint Mary’s Hospital, Seoul, South Korea
  112. (112) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  113. (113) University of Oslo, grid.5510.1
  114. (114) Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong
  115. (115) University of Hong Kong, grid.194645.b
  116. (116) Flanders Institute for Biotechnology, grid.11486.3a
  117. (117) KU Leuven, grid.5596.f
  118. (118) University of Hawaii at Manoa, grid.410445.0
  119. (119) Soonchunhyang University Hospital, grid.412678.e
  120. (120) Asan Medical Center, grid.413967.e
  121. (121) Technion – Israel Institute of Technology, grid.6451.6
  122. (122) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  123. (123) German Breast group, grid.434440.3
  124. (124) University of Manchester, grid.5379.8
  125. (125) University of Warwick, grid.7372.1
  126. (126) Macedonian Academy of Sciences and Arts, grid.419383.4
  127. (127) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  128. (128) Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  129. (129) Cancer Research Malaysia, grid.507182.9
  130. (130) The Alfred Hospital, grid.1623.6
  131. (131) Technical University of Munich, grid.6936.a
  132. (132) Hospital Monte Naranco, grid.414858.4
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  134. (134) University Malaya Medical Centre, grid.413018.f
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  138. (138) Center for Clinical Cancer Genetics and Global Health, The University of Chicago, Chicago, Illinois, USA
  139. (139) University of New Mexico, grid.266832.b
  140. (140) IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  141. (141) Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Australia
  142. (142) Peter MacCallum Cancer Centre, grid.1055.1
  143. (143) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
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  146. (146) Hospital Universitario Puerta de Hierro Majadahonda, grid.73221.35
  147. (147) Städtisches Klinikum Karlsruhe, grid.419594.4
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  149. (149) National Cancer Institute of Thailand, grid.419173.9
  150. (150) King's College London, grid.13097.3c
  151. (151) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  152. (152) Case Western Reserve University, grid.67105.35
  153. (153) John Hunter Hospital, grid.414724.0
  154. (154) University of Newcastle Australia, grid.266842.c
  155. (155) University of Kansas Medical Center, grid.412016.0
  156. (156) China Medical University, grid.254145.3
  157. (157) University of British Columbia, grid.17091.3e
  158. (158) Krebsregister Saarland, grid.482902.5
  159. (159) Royal Women's Hospital, grid.416259.d
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  161. (161) Columbia University, grid.21729.3f
  162. (162) Ministry of Public Health, grid.415836.d
  163. (163) University of Oxford, grid.4991.5
  164. (164) Pontificia Universidad Javeriana, grid.41312.35
  165. (165) Klinikum Mittelbaden, grid.506801.a
  166. (166) Cancer Registry of Norway, grid.418941.1
  167. (167) Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany
  168. (168) University Medical Center Utrecht, grid.7692.a
  169. (169) University of Ulm, grid.6582.9
  170. (170) Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA
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  175. (175) University of California, San Francisco, grid.266102.1
  176. (176) Royal Brisbane and Women's Hospital, grid.416100.2
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  178. (178) University Cancer Center Hamburg, grid.412315.0
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Description

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.

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University of Copenhagen

Danish Open Access Indicator

2017: Unused

Research area: Medicine

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2017: Level 2

Research area: Medicine

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Times Cited: 402

Field Citation Ratio (FCR): 101.99

Relative Citation ratio (RCR): 22.04

Open Access Info

Green, Accepted