Article open access publication

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

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 7, 1, 2016

DOI:10.1038/ncomms11375, Dimensions: pub.1007139031, PMC: PMC4853421, PMID: 27117709,

Authors

Ahsan, Habibul (6) (7) (8)
Andrulis, Irene L. (11) (12)
Benitez, Javier (21) (22)
Brauch, Hiltrud (27) (28)
Ehrencrona, Hans (50) (51)
Ekici, Arif B. (52) (53)
Eliassen, Heather (54) (55)
Försti, Asta (14) (57)
Goldberg, Mark S (59) (70)
James, Paul (80) (83)
Kwong, Ava (92) (93)
Malone, Kathleen E (100) (101)
Mulligan, Anna M. (11) (105)
Muranen, Taru A (9) (29)
Olah, Edith (108)
Park, Sue K. (110)
Peeters, Petra H M (73) (111)
Rennert, Gad (116)
Robson, Mark (107)
Sanchez, Maria-Jose (119) (120)
Schmutzler, Rita K. (122) (123)
Sinilnikova, Olga M (40) (126)
Soucy, Penny (125)
Tamimi, Rulla (54) (55)
Teixeira, Manuel R. (131) (132)
Teo, Soo-Hwang (133) (134)
Tung, Nadine (139)
Ursin, Giski (140)
Weiderpass, Elisabete (38) (140) (143) (144)
Yao, Song (10)
Zheng, Wei (99)
Hall, Per (38)

* Corresponding author

Affiliations

Organisations

  1. (1) Mayo Clinic, grid.66875.3a
  2. (2) University of Cambridge, grid.5335.0
  3. (3) Moffitt Cancer Center, grid.468198.a
  4. (4) Oslo University Hospital, grid.55325.34
  5. (5) Istituto Oncologico Veneto, grid.419546.b
  6. (6) Comprehensive Cancer Center, The University of Chicago, 60637, Chicago, Illinois, USA
  7. (7) Departments of Medicine and Human Genetics, The University of Chicago, 60637, Chicago, Illinois, USA
  8. (8) University of Chicago, grid.170205.1
  9. (9) Helsinki University Central Hospital, grid.15485.3d
  10. (10) Roswell Park Cancer Institute, grid.240614.5
  11. (11) University of Toronto, grid.17063.33
  12. (12) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  13. (13) University of California, Irvine, grid.266093.8
  14. (14) German Cancer Research Center, grid.7497.d
  15. (15) The University of Texas MD Anderson Cancer Center, grid.240145.6
  16. (16) Karolinska University Hospital, grid.24381.3c
  17. (17) European Institute of Oncology, grid.15667.33
  18. (18) Department of Pathology, Landspitali University Hospital and University of Iceland School of Medicine, 101, Reykjavik, Iceland
  19. (19) Institute for Quality and Efficiency in Health Care, grid.414694.a
  20. (20) Department of Gynecology and Obstetrics, University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, 91054, Erlangen, Germany
  21. (21) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  22. (22) Spanish National Cancer Research Centre, grid.7719.8
  23. (23) New York University, grid.137628.9
  24. (24) Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00029, Helsinki, Finland
  25. (25) Hannover Medical School, grid.10423.34
  26. (26) Herlev Hospital, grid.411900.d, Capital Region
  27. (27) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  28. (28) University of Tübingen, grid.10392.39
  29. (29) Heidelberg University, grid.7700.0
  30. (30) University of Utah, grid.223827.e
  31. (31) Hospital Clínico San Carlos, grid.411068.a
  32. (32) Department of Laboratory Medicine, Section of Genetic Oncology, University and University Hospital of Pisa, I-56126, Pisa, Italy
  33. (33) University of Sydney, grid.1013.3
  34. (34) National Cancer Institute, grid.48336.3a
  35. (35) Columbia University, grid.21729.3f
  36. (36) Ghent University, grid.5342.0
  37. (37) University of Sheffield, grid.11835.3e
  38. (38) Karolinska Institute, grid.4714.6
  39. (39) Temple University Health System, grid.412530.1
  40. (40) University of Lyon System, grid.25697.3f
  41. (41) Leiden University Medical Center, grid.10419.3d
  42. (42) Hospital Universitari Vall d'Hebron, grid.411083.f
  43. (43) City Of Hope National Medical Center, grid.410425.6
  44. (44) Cancer Bioimmunotherapy Unit, CRO Aviano National Cancer Institute, 33081, Aviano, Italy
  45. (45) University of Pennsylvania, grid.25879.31
  46. (46) University of Pretoria, grid.49697.35
  47. (47) London School of Hygiene & Tropical Medicine, grid.8991.9
  48. (48) Centre Hospitalier Universitaire de Québec, grid.411081.d
  49. (49) Faculty of Medicine, University of Southampton, University Hospital Southampton, SO16 6YD, Southampton, Hampshire, UK
  50. (50) Skåne University Hospital, grid.411843.b
  51. (51) Uppsala University, grid.8993.b
  52. (52) Comprehensive Cancer Center -EMN, 91054, Erlangen, Germany
  53. (53) Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, 91054, Erlangen, Germany
  54. (54) Harvard University, grid.38142.3c
  55. (55) Brigham and Women's Hospital, grid.62560.37
  56. (56) University Medical Center Hamburg-Eppendorf, grid.13648.38
  57. (57) Lund University, grid.4514.4
  58. (58) National Centre of Scientific Research Demokritos, grid.6083.d
  59. (59) McGill University, grid.14709.3b
  60. (60) University of, 19104, Philadelphia, Pennsylvania, USA
  61. (61) Sheba Medical Center, grid.413795.d
  62. (62) Department of Epidemiology, University of, 27599-7400, Chapel Hill, North Carolina, USA
  63. (63) University of California, Los Angeles, grid.19006.3e
  64. (64) American Cancer Society, grid.422418.9
  65. (65) Dana-Farber Cancer Institute, grid.65499.37
  66. (66) Cedars-Sinai Medical Center, grid.50956.3f
  67. (67) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark
  68. (68) Cancer Council Victoria, grid.3263.4
  69. (69) University of Kansas Medical Center, grid.412016.0
  70. (70) Royal Victoria Hospital, grid.416229.a
  71. (71) Pomeranian Medical University, grid.107950.a
  72. (72) French Institute of Health and Medical Research, grid.7429.8
  73. (73) Imperial College London, grid.7445.2
  74. (74) University of Southern California, grid.42505.36
  75. (75) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark
  76. (76) QIMR Berghofer Medical Research Institute, grid.1049.c
  77. (77) Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, 91010, Duarte, California, USA
  78. (78) Antoni van Leeuwenhoek Hospital, grid.430814.a
  79. (79) Erasmus University Medical Center, grid.5645.2
  80. (80) University of Melbourne, grid.1008.9
  81. (81) Institute of Oncology NN Petrov, grid.465337.0
  82. (82) Georgetown University Medical Center, grid.411667.3
  83. (83) Peter MacCallum Cancer Centre, grid.1055.1
  84. (84) State Research Institute Centre for Innovative Medicine, grid.493509.2
  85. (85) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  86. (86) Cancer Prevention Institute of California, grid.280669.3
  87. (87) Institute of Cancer Research, grid.18886.3f
  88. (88) Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, FI-00029, Helsinki, Finland
  89. (89) Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, M5G 1X5, Toronto, Ontario, Canada
  90. (90) Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53113, Bonn, Germany
  91. (91) University of Eastern Finland, grid.9668.1
  92. (92) Hong Kong Sanatorium and Hospital, grid.414329.9
  93. (93) University of Hong Kong, grid.194645.b
  94. (94) Flanders Institute for Biotechnology, grid.11486.3a
  95. (95) Catalan Institute of Oncology, grid.418701.b
  96. (96) Cancer Epidemiology Program, University of Cancer Center, 96813, Honolulu, Hawaii, USA
  97. (97) Mayo Clinic, grid.417468.8
  98. (98) Genome Institute of Singapore, grid.418377.e
  99. (99) Vanderbilt University, grid.152326.1
  100. (100) Fred Hutchinson Cancer Research Center, grid.270240.3
  101. (101) University of Washington, grid.34477.33
  102. (102) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  103. (103) Technical University of Munich, grid.6936.a
  104. (104) Case Western Reserve University, grid.67105.35
  105. (105) University Health Network, grid.231844.8
  106. (106) Invitae Corporation, 94107, San Francisco, California, USA
  107. (107) Memorial Sloan Kettering Cancer Center, grid.51462.34
  108. (108) National Institute of Oncology, grid.419617.c
  109. (109) University of Chicago Medical Center, grid.412578.d
  110. (110) Seoul National University, grid.31501.36
  111. (111) University Medical Center Utrecht, grid.7692.a
  112. (112) FIRC Institute of Molecular Oncology, grid.7678.e
  113. (113) The Ohio State University, grid.261331.4
  114. (114) University of Oulu, grid.10858.34
  115. (115) Medical University of Vienna, grid.22937.3d
  116. (116) Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, 34362, Haifa, Israel
  117. (117) Johns Hopkins University, grid.21107.35
  118. (118) International Agency For Research On Cancer, grid.17703.32
  119. (119) Andalusian School of Public Health, grid.413740.5
  120. (120) Institute of Health Carlos III, grid.413448.e
  121. (121) King's College London, grid.13097.3c
  122. (122) University Hospital Cologne, grid.411097.a
  123. (123) University of Cologne, grid.6190.e
  124. (124) John Hunter Hospital, grid.414724.0
  125. (125) Laval University, grid.23856.3a
  126. (126) Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon—Centre Léon Bérard, 69373, Lyon, France
  127. (127) Linköping University, grid.5640.7
  128. (128) Institute Curie, grid.418596.7
  129. (129) Paris Descartes University, grid.10992.33
  130. (130) National Human Genome Research Institute, grid.280128.1
  131. (131) Portuguese Oncology Institute, grid.418711.a
  132. (132) University of Porto, grid.5808.5
  133. (133) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500, Subang Jaya, Malaysia
  134. (134) University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, 50603, Kuala Lumpur, Malaysia
  135. (135) Odense University Hospital, grid.7143.1, Southern Denmark Region
  136. (136) Latvian Biomedical Research and Study Centre, grid.419210.f
  137. (137) University of Oxford, grid.4991.5
  138. (138) Cancer Registry and Histopathology Unit, ‘Civic—M.P. Arezzo’ Hospital, 97100, ASP Ragusa, Italy
  139. (139) Beth Israel Deaconess Medical Center, grid.239395.7
  140. (140) Cancer Registry of Norway, grid.418941.1
  141. (141) Charité, grid.6363.0
  142. (142) University Hospital Ulm, grid.410712.1
  143. (143) Folkhälsans Forskningscentrum, grid.428673.c
  144. (144) The Arctic University of Norway, grid.10919.30
  145. (145) Stanford University, grid.168010.e
  146. (146) Universitair Ziekenhuis Leuven, grid.410569.f
  147. (147) Hospital Universitario La Paz, grid.81821.32

Description

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

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2016: Realized

Research area: Medicine

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Research area: Medicine

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Times Cited: 48

Field Citation Ratio (FCR): 9.98

Relative Citation ratio (RCR): 2.4

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