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