Article open access publication

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 49, 12, 2017

DOI:10.1038/ng.3785, Dimensions: pub.1092350084, PMC: PMC5808456, PMID: 29058716,

Authors

Milne, Roger L * (1) (2)
Finucane, Hilary (8) (11)
Wang, Qin (4)
Auer, Paul L (27) (28)
Benitez, Javier (38) (39)
Blot, William (45) (46)
Boeckx, Bram (47) (48)
Bojesen, Stig E (50) (51) (52)
Brauch, Hiltrud (23) (57) (58)
Burwinkel, Barbara (23) (67)
Campbell, Ian (2) (71)
Carracedo, Angel (72) (73)
Cox, David G (88) (89)
Dicks, Ed (4)
Eeles, Ros (100)
Faivre, Laurence (106) (107)
Fasching, Peter A (37) (108)
Figueroa, Jonine (61) (109)
Friedman, Eitan (114) (115)
Garber, Judy (119)
Giles, Graham G (1) (2)
Grip, Mervi (127)
Grundy, Anne (129)
Guo, Qi (4)
Hahnen, Eric (131) (132)
Hartikainen, Jaana M (136) (137)
Hulick, Peter J (142) (143)
James, Paul (2) (71)
John, Esther M (151) (152)
Kast, Karin (155)
Khan, Sofia (159)
Khusnutdinova, Elza (40) (160)
Knight, Julia A (9) (20)
Kosma, Veli-Matti (136) (137)
Kristensen, Vessela N (53) (162) (163)
Kwong, Ava (165) (166) (167)
Lee, Eunjung (133)
Lesueur, Fabienne (77) (175) (176)
Lo, Wing-Yee (57) (58)
Matsuo, Keitaro (183) (184)
Miao, Hui (189)
Muir, Kenneth (190) (191)
Nielsen, Sune F (50) (51)
Nordestgaard, Børge G (50) (51) (52)
Ong, Kai-ren (196)
Orr, Nick (111)
Osorio, Ana (38) (39)
Papi, Laura (199)
Peixoto, Ana (202)
Pylkäs, Katri (207) (208)
Rack, Brigitte (94) (149)
Rennert, Gad (170) (210)
Rennert, Hedy S (170) (210)
Rhiem, Kerstin (131) (132)
Romero, Atocha (69) (212)
Romm, Jane (13)
Scott, Rodney J (218) (219)
Seal, Sheila (111)
Shen, Chen-Yang (221) (222)
Sheng, Xin (133)
Side, Lucy E (223)
Spinelli, John J (64) (225)
Surowy, Harald (23) (67)
Tamimi, Rulla M (8) (104)
Tan, Yen Y (130)
Tengström, Maria (136) (137)
Teo, Soo H (230) (231)
Teulé, Alex (233)
Tischkowitz, Marc (113) (237)
Tong, Ling (16)
Torres, Diana (23) (239)
Tung, Nadine (241)
Vega, Ana (72) (245)
Walker, Lisa (247)
Wang, Zhaoming (61) (248)
Wijnen, Juul T (93) (141)
Winqvist, Robert (207) (208)
Wu, Anna H (133)
Xia, Lucy (133)
Zheng, Wei (46)
Zhu, Bin (61)
Ziv, Elad (78)
Mannermaa, Arto (136) (137)
Teixeira, Manuel R (202) (249)
Stone, Jennifer (139) (250)
Park, Sue K (154)
Hall, Per (56) (252)
Schmutzler, Rita K (131) (132)

* Corresponding author

Affiliations

Organisations

  1. (1) Cancer Council Victoria, grid.3263.4
  2. (2) University of Melbourne, grid.1008.9
  3. (3) Wellcome Sanger Institute, grid.10306.34
  4. (4) University of Cambridge, grid.5335.0
  5. (5) Cyprus Institute of Neurology and Genetics, grid.417705.0
  6. (6) QIMR Berghofer Medical Research Institute, grid.1049.c
  7. (7) University of Washington, grid.34477.33
  8. (8) Harvard University, grid.38142.3c
  9. (9) University of Toronto, grid.17063.33
  10. (10) Laval University, grid.23856.3a
  11. (11) Massachusetts Institute of Technology, grid.116068.8
  12. (12) Academic Medical Center, grid.5650.6
  13. (13) Johns Hopkins University, grid.21107.35
  14. (14) Chapel Allerton Hospital, grid.413818.7
  15. (15) Istituto Oncologico Veneto, grid.419546.b
  16. (16) Center for Cancer Epidemiology and Prevention, University of Chicago, Chicago, Illinois, USA
  17. (17) Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  18. (18) Roswell Park Cancer Institute, grid.240614.5
  19. (19) Dartmouth College, grid.254880.3
  20. (20) Mount Sinai Hospital, grid.416166.2
  21. (21) University of California, Irvine, grid.266093.8
  22. (22) N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
  23. (23) German Cancer Research Center, grid.7497.d
  24. (24) Institute of Clinical Molecular Biology / Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany
  25. (25) Queen's University, grid.410356.5
  26. (26) Hannover Medical School, grid.10423.34
  27. (27) University of Wisconsin–Milwaukee, grid.267468.9
  28. (28) Fred Hutchinson Cancer Research Center, grid.270240.3
  29. (29) University Medical Center Utrecht, grid.7692.a
  30. (30) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  31. (31) McGill University and Génome Québec Innovation Centre, grid.411640.6
  32. (32) Hospital Universitari Vall d'Hebron, grid.411083.f
  33. (33) European Institute of Oncology, grid.15667.33
  34. (34) Centre Léon Bérard, grid.418116.b
  35. (35) National University Hospital of Iceland, grid.410540.4
  36. (36) University of Iceland, grid.14013.37
  37. (37) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  38. (38) Spanish National Cancer Research Centre, grid.7719.8
  39. (39) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  40. (40) Institute of Biochemistry and Genetics of Ufa Scientific Centre, grid.429129.5
  41. (41) City Of Hope National Medical Center, grid.410425.6
  42. (42) Université Clermont Auvergne, INSERM, U1240, Imagerie Moléculaire et Stratégies Théranostiques, Centre Jean Perrin, Clermont-Ferrand, France
  43. (43) Maastricht University Medical Centre, grid.412966.e
  44. (44) Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  45. (45) International Epidemiology Institute, grid.419344.f
  46. (46) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  47. (47) Flanders Institute for Biotechnology, grid.11486.3a
  48. (48) KU Leuven, grid.5596.f
  49. (49) Vejle Sygehus, grid.417271.6, Southern Denmark Region
  50. (50) Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  51. (51) Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  52. (52) University of Copenhagen, grid.5254.6, KU
  53. (53) Oslo University Hospital, grid.55325.34
  54. (54) National Institute of Oncology, grid.419617.c
  55. (55) Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
  56. (56) Karolinska Institute, grid.4714.6
  57. (57) University of Tübingen, grid.10392.39
  58. (58) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  59. (59) Institut Gustave Roussy, grid.14925.3b
  60. (60) Royal Devon and Exeter Hospital, grid.416118.b
  61. (61) National Cancer Institute, grid.48336.3a
  62. (62) Lund University, grid.4514.4
  63. (63) Simon Fraser University, grid.61971.38
  64. (64) BC Cancer Agency, grid.248762.d
  65. (65) Catalan Institute of Oncology, grid.418701.b
  66. (66) Ruhr University Bochum, grid.5570.7
  67. (67) Heidelberg University, grid.7700.0
  68. (68) Huntsman Cancer Institute, grid.479969.c
  69. (69) Hospital Clínico San Carlos, grid.411068.a
  70. (70) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  71. (71) Peter MacCallum Cancer Centre, grid.1055.1
  72. (72) University of Santiago de Compostela, grid.11794.3a
  73. (73) Complejo Hospitalario Universitario de Santiago, grid.411048.8
  74. (74) American Cancer Society, grid.422418.9
  75. (75) Oncology and Genetics Unit, Instituto de Investigación Biomédica (IBI) de Orense-Pontevedra-Vigo, Xerencia de Xestión Integrada de Vigo, Servizo Galego de Saúde SERGAS, Vigo, Spain
  76. (76) UniCancer Group, grid.418189.d
  77. (77) Institute Curie, grid.418596.7
  78. (78) University of California, San Francisco, grid.266102.1
  79. (79) University Cancer Center Hamburg, grid.412315.0
  80. (80) Hôpital du Saint-Sacrement, grid.416673.1
  81. (81) Ghent University, grid.5342.0
  82. (82) University of Sydney, grid.1013.3
  83. (83) Sheffield Children's Hospital, grid.413991.7
  84. (84) Cancer and Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  85. (85) Antoni van Leeuwenhoek Hospital, grid.430814.a
  86. (86) Hôpital Arnaud De Villeneuve, grid.413745.0
  87. (87) University of Sheffield, grid.11835.3e
  88. (88) Cancer Center of Lyon, grid.462282.8
  89. (89) Imperial College London, grid.7445.2
  90. (90) Mayo Clinic, grid.66875.3a
  91. (91) Temple University Health System, grid.412530.1
  92. (92) University of Glasgow, grid.8756.c
  93. (93) Leiden University Medical Center, grid.10419.3d
  94. (94) Ludwig Maximilian University of Munich, grid.5252.0
  95. (95) University of Pretoria, grid.49697.35
  96. (96) London School of Hygiene & Tropical Medicine, grid.8991.9
  97. (97) University of Southampton, grid.5491.9
  98. (98) University of Westminster, grid.12896.34
  99. (99) University of Münster, grid.5949.1
  100. (100) Royal Marsden NHS Foundation Trust, grid.5072.0
  101. (101) Skåne University Hospital, grid.411843.b
  102. (102) Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  103. (103) Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  104. (104) Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  105. (105) Leipzig University, grid.9647.c
  106. (106) Centre Georges François Leclerc, grid.418037.9
  107. (107) Centre Hospitalier Regional Universitaire De Dijon, grid.31151.37
  108. (108) University of California, Los Angeles, grid.19006.3e
  109. (109) University of Edinburgh, grid.4305.2
  110. (110) University Medical Center Hamburg-Eppendorf, grid.13648.38
  111. (111) Institute of Cancer Research, grid.18886.3f
  112. (112) Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  113. (113) McGill University, grid.14709.3b
  114. (114) Tel Aviv University, grid.12136.37
  115. (115) Sheba Medical Center, grid.413795.d
  116. (116) Curtin University, grid.1032.0
  117. (117) Memorial Sloan Kettering Cancer Center, grid.51462.34
  118. (118) University of North Carolina at Chapel Hill, grid.10698.36
  119. (119) Dana-Farber Cancer Institute, grid.65499.37
  120. (120) University of Würzburg, grid.8379.5
  121. (121) University Hospital of Heraklion, grid.412481.a
  122. (122) Rigshospitalet, grid.475435.4, Capital Region
  123. (123) University of Kansas Medical Center, grid.412016.0
  124. (124) University of Utah, grid.223827.e
  125. (125) Department of Obstetrics and Gynecology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, USA
  126. (126) National Institutes of Health, grid.94365.3d
  127. (127) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  128. (128) Pomeranian Medical University, grid.107950.a
  129. (129) Centre Hospitalier de l’Université de Montréal, grid.410559.c
  130. (130) Medical University of Vienna, grid.22937.3d
  131. (131) University Hospital Cologne, grid.411097.a
  132. (132) University of Cologne, grid.6190.e
  133. (133) University of Southern California, grid.42505.36
  134. (134) University of Massachusetts Amherst, grid.266683.f
  135. (135) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  136. (136) Kuopio University Hospital, grid.410705.7
  137. (137) University of Eastern Finland, grid.9668.1
  138. (138) Institute of Genetic Medicine, Centre for Life, Newcastle-upon-Tyne Hospitals NHS Trust, Newcastle-upon-Tyne, UK
  139. (139) University of Western Australia, grid.1012.2
  140. (140) University College London, grid.83440.3b
  141. (141) Erasmus University Medical Center, grid.5645.2
  142. (142) Pritzker School of Medicine, University of Chicago, Evanston, Illinois, USA
  143. (143) NorthShore University HealthSystem, grid.240372.0
  144. (144) Institute of Oncology NN Petrov, grid.465337.0
  145. (145) Georgetown University Medical Center, grid.411667.3
  146. (146) National Cancer Centre, grid.272242.3
  147. (147) Guy's and St Thomas' NHS Foundation Trust, grid.420545.2
  148. (148) State Research Institute Centre for Innovative Medicine, grid.493509.2
  149. (149) University of Ulm, grid.6582.9
  150. (150) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  151. (151) Cancer Prevention Institute of California, grid.280669.3
  152. (152) Stanford University, grid.168010.e
  153. (153) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
  154. (154) Seoul National University, grid.31501.36
  155. (155) TU Dresden, grid.4488.0
  156. (156) National University of Ireland, Galway, grid.6142.1
  157. (157) Radboud University Nijmegen Medical Centre, grid.10417.33
  158. (158) Universitair Ziekenhuis Leuven, grid.410569.f
  159. (159) Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  160. (160) Bashkir State University, grid.77269.3d
  161. (161) National Centre of Scientific Research Demokritos, grid.6083.d
  162. (162) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
  163. (163) University of Oslo, grid.5510.1
  164. (164) Odense University Hospital, grid.7143.1, Southern Denmark Region
  165. (165) Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong
  166. (166) Hong Kong Sanatorium and Hospital, grid.414329.9
  167. (167) University of Hong Kong, grid.194645.b
  168. (168) Department of Pathology, Division Slagelse, University Hospital of Region Zealand, Slagelse, Denmark
  169. (169) Manchester University NHS Foundation Trust, grid.498924.a
  170. (170) Clalit National Cancer Control Center, Haifa, Israel
  171. (171) Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain
  172. (172) University of Hawaii at Manoa, grid.410445.0
  173. (173) Asan Medical Center, grid.413967.e
  174. (174) Soonchunhyang University Hospital, grid.412678.e
  175. (175) Mines Paris Tech, Fontainebleau, France
  176. (176) PSL Research University, grid.440907.e
  177. (177) Mayo Clinic, grid.417468.8
  178. (178) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  179. (179) German Breast group, grid.434440.3
  180. (180) Macedonian Academy of Sciences and Arts, grid.419383.4
  181. (181) Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  182. (182) University of California, San Diego, grid.266100.3
  183. (183) Aichi Cancer Center, grid.410800.d
  184. (184) Nagoya University, grid.27476.30
  185. (185) University of Lyon System, grid.25697.3f
  186. (186) The Alfred Hospital, grid.1623.6
  187. (187) VU University Medical Center, grid.16872.3a
  188. (188) Hospital Monte Naranco, grid.414858.4
  189. (189) National University of Singapore, grid.4280.e
  190. (190) University of Manchester, grid.5379.8
  191. (191) University of Warwick, grid.7372.1
  192. (192) University Health Network, grid.231844.8
  193. (193) Sorbonne University, grid.462844.8
  194. (194) Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  195. (195) Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, Illinois, USA
  196. (196) West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK
  197. (197) Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  198. (198) University of New Mexico, grid.266832.b
  199. (199) University of Florence, grid.8404.8
  200. (200) Uppsala University, grid.8993.b
  201. (201) Aalborg Hospital, grid.27530.33, North Denmark Region
  202. (202) Portuguese Oncology Institute, grid.418711.a
  203. (203) IFOM, FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  204. (204) Moffitt Cancer Center, grid.468198.a
  205. (205) Western General Hospital, grid.417068.c
  206. (206) ProCURE, Catalan Institute of Oncology, IDIBELL (Bellvitge Biomedical Research Institute), Barcelona, Spain
  207. (207) Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
  208. (208) University of Oulu, grid.10858.34
  209. (209) Karolinska University Hospital, grid.24381.3c
  210. (210) Carmel Medical Center, grid.413469.d
  211. (211) Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  212. (212) Hospital Universitario Puerta de Hierro Majadahonda, grid.73221.35
  213. (213) Städtisches Klinikum Karlsruhe, grid.419594.4
  214. (214) National Institute of Environmental Health Sciences, grid.280664.e
  215. (215) National Cancer Institute of Thailand, grid.419173.9
  216. (216) Case Western Reserve University, grid.67105.35
  217. (217) King's College London, grid.13097.3c
  218. (218) John Hunter Hospital, grid.414724.0
  219. (219) University of Newcastle Australia, grid.266842.c
  220. (220) The Ohio State University, grid.261331.4
  221. (221) China Medical University, grid.254145.3
  222. (222) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  223. (223) Great Ormond Street Hospital for Children NHS Foundation Trust, grid.424537.3
  224. (224) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  225. (225) University of British Columbia, grid.17091.3e
  226. (226) Krebsregister Saarland, grid.482902.5
  227. (227) University Hospital Heidelberg, grid.5253.1
  228. (228) National Human Genome Research Institute, grid.280128.1
  229. (229) BioCruces Health research Institute, grid.452310.1
  230. (230) Cancer Research Malaysia, grid.507182.9
  231. (231) University Malaya Medical Centre, grid.413018.f
  232. (232) Columbia University, grid.21729.3f
  233. (233) Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain
  234. (234) Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  235. (235) Ospedale di Circolo e Fondazione Macchi, grid.412972.b
  236. (236) Latvian Biomedical Research and Study Centre, grid.419210.f
  237. (237) Addenbrooke's Hospital, grid.120073.7
  238. (238) University of Oxford, grid.4991.5
  239. (239) Pontificia Universidad Javeriana, grid.41312.35
  240. (240) Prince of Wales Hospital, grid.415193.b
  241. (241) Beth Israel Deaconess Medical Center, grid.239395.7
  242. (242) Frauenklinik der Stadtklinik Baden Baden, Baden Baden, Germany
  243. (243) Ospedale San Martino, grid.410345.7
  244. (244) Charité, grid.6363.0
  245. (245) Fundación Pública Galega de Medicina Xenómica, grid.443929.1
  246. (246) Centro di Riferimento Oncologico, grid.418321.d
  247. (247) Churchill Hospital, grid.415719.f
  248. (248) St. Jude Children's Research Hospital, grid.240871.8
  249. (249) University of Porto, grid.5808.5
  250. (250) Royal Women's Hospital, grid.416259.d
  251. (251) Sapienza University of Rome, grid.7841.a
  252. (252) Department of Oncology, South General Hospital, Stockholm, Sweden
  253. (253) Technical University of Munich, grid.6936.a

Description

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

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2017: Realized

Research area: Medicine

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2017: Level 2

Research area: Medicine

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Times Cited: 119

Field Citation Ratio (FCR): 30.92

Relative Citation ratio (RCR): 6.13

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