Article
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
Affiliations
Organisations
- (1) University of Cambridge, grid.5335.0
- (2) QIMR Berghofer Medical Research Institute, grid.1049.c
- (3) Institute of Cancer Research, grid.18886.3f
- (4) University of Southern California, grid.42505.36
- (5) Harvard University, grid.38142.3c
- (6) University of Sydney, grid.1013.3
- (7) Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts
- (8) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
- (9) University of Surrey, grid.5475.3
- (10) German Cancer Research Center, grid.7497.d
- (11) University College London, grid.83440.3b
- (12) Stanford University, grid.168010.e
- (13) Karolinska Institute, grid.4714.6
- (14) Moffitt Cancer Center, grid.468198.a
- (15) Portuguese Oncology Institute, grid.418711.a
- (16) University of Sheffield, grid.11835.3e
- (17) Spanish National Cancer Research Centre, grid.7719.8
- (18) A list of members from the Australian Ovarian Cancer Study (AOCS) Study Group and the Australian Cancer Study (Ovarian Cancer) is provided in the Acknowledgments
- (19) A list of members from the Australian Prostate Cancer BioResource (APCB) BioResource is provided in the Acknowledgments
- (20) Queensland University of Technology, grid.1024.7
- (21) University of California, Irvine, grid.266093.8
- (22) University Hospital Erlangen, Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
- (23) Cedars-Sinai Medical Center, grid.50956.3f
- (24) Herlev Hospital, grid.411900.d, Capital Region
- (25) University of Helsinki, grid.7737.4
- (26) The Alfred Hospital, grid.1623.6
- (27) University of Michigan, grid.214458.e
- (28) Mayo Clinic, grid.66875.3a
- (29) Pomeranian Medical University, grid.107950.a
- (30) Medical University of Sofia, grid.410563.5
- (31) Krebsregister Saarland, grid.482902.5
- (32) University Hospital Ulm, grid.410712.1
- (33) Roswell Park Cancer Institute, grid.240614.5
- (34) The Juliane Marie Centre, Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- (35) University of Utah, grid.223827.e
- (36) Seoul National University, grid.31501.36
- (37) McGill University and Génome Québec Innovation Centre, grid.411640.6
- (38) Brigham and Women's Hospital, grid.62560.37
- (39) Cancer Research UK Cambridge Institute, grid.470869.4
- (40) University of Southampton, grid.5491.9
- (41) University Medical Center Hamburg-Eppendorf, grid.13648.38
- (42) Vanderbilt University Medical Center, grid.412807.8
- (43) Memorial Sloan Kettering Cancer Center, grid.51462.34
- (44) National Centre of Scientific Research Demokritos, grid.6083.d
- (45) King's College London, grid.13097.3c
- (46) Rutgers, The State University of New Jersey, grid.430387.b
- (47) Bashkir State University, grid.77269.3d
- (48) Institute of Biochemistry and Genetics of Ufa Scientific Centre, grid.429129.5
- (49) University of Copenhagen, grid.5254.6, KU
- (50) Danish Cancer Society, grid.417390.8
- (51) Tianjin Medical University Cancer Institute and Hospital, grid.411918.4
- (52) Cancer Council Victoria, grid.3263.4
- (53) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
- (54) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
- (55) University of Pittsburgh, grid.21925.3d
- (56) University of Pittsburgh Cancer Institute, grid.478063.e
- (57) Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK
- (58) University of Oxford, grid.4991.5
- (59) Monash University, grid.1002.3
- (60) University of Melbourne, grid.1008.9
- (61) Skåne University Hospital, grid.411843.b
- (62) Universitair Ziekenhuis Leuven, grid.410569.f
- (63) Klinikum Mittelbaden, grid.506801.a
- (64) Yale University, grid.47100.32
- (65) Haukeland University Hospital, grid.412008.f
- (66) University of Bergen, grid.7914.b
- (67) University Hospital Heidelberg, grid.5253.1
- (68) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
- (69) University of Tübingen, grid.10392.39
- (70) University of Glasgow, grid.8756.c
- (71) Peter MacCallum Cancer Centre, grid.1055.1
- (72) Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
- (73) Fred Hutchinson Cancer Research Center, grid.270240.3
- (74) University of Washington, grid.34477.33
- (75) Dartmouth College, grid.254880.3
- (76) University of Bristol, grid.5337.2
- (77) Duke University, grid.26009.3d
- (78) Duke University Hospital, grid.189509.c
- (79) Tampere University, grid.502801.e
- (80) University of Turku, grid.1374.1
- (81) National Institutes of Health, grid.94365.3d
- (82) Mount Sinai Hospital, grid.416166.2
- (83) University of Toronto, grid.17063.33
- (84) London School of Hygiene & Tropical Medicine, grid.8991.9
- (85) The University of Texas MD Anderson Cancer Center, grid.240145.6
- (86) Rechts der Isar Hospital, grid.15474.33
- (87) A list of members from the Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer (kConFab) Investigators is provided in the Acknowledgments
- (88) Kyushu University, grid.177174.3
- (89) University of Manchester, grid.5379.8
- (90) University of Warwick, grid.7372.1
- (91) Radboud University Nijmegen Medical Centre, grid.10417.33
- (92) University of New Mexico, grid.266832.b
- (93) George E. Wahlen Department of VA Medical Center, grid.413886.0
- (94) Erasmus University Medical Center, grid.5645.2
- (95) University of Porto, grid.5808.5
- (96) Antoni van Leeuwenhoek Hospital, grid.430814.a
- (97) Danderyds sjukhus, grid.412154.7
- (98) Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (99) KU Leuven, grid.5596.f
- (100) Meharry Medical College, grid.259870.1
- (101) Cancer Center and Department of Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- (102) Hannover Medical School, grid.10423.34
- (103) A list of members from the Norwegian Breast Cancer Study (NBCS) Investigators is provided in the Acknowledgments
- (104) BC Cancer Agency, grid.248762.d
- (105) FIRC Institute of Molecular Oncology, grid.7678.e
- (106) French Institute of Health and Medical Research, grid.7429.8
- (107) University of Paris-Sud, grid.5842.b
- (108) International Agency For Research On Cancer, grid.17703.32
- (109) Leiden University Medical Center, grid.10419.3d
- (110) Vanderbilt University, grid.152326.1
- (111) Xiamen University, grid.12955.3a
- (112) Dana-Farber Cancer Institute, grid.65499.37
- (113) University Hospital Cologne, grid.411097.a
- (114) University of Cologne, grid.6190.e
- (115) University of Oulu, grid.10858.34
- (116) The University of Texas Health Science Center at Houston, grid.267308.8
- (117) National University Health System, grid.410759.e
- (118) National University of Singapore, grid.4280.e
- (119) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
- (120) University of Malaya Cancer Research Institute, University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia
- (121) American Cancer Society, grid.422418.9
- (122) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- (123) Oregon Health & Science University, grid.5288.7
- (124) A list of members from the GENICA Network is provided in the Acknowledgments
- (125) A list of members from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium is provided in the Acknowledgments
- (126) Ruhr University Bochum, grid.5570.7
- (127) Kuopio University Hospital, grid.410705.7
- (128) University of Eastern Finland, grid.9668.1
- (129) Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
- (130) K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- (131) Oslo University Hospital, grid.55325.34
- (132) Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
- (133) Shanghai Cancer Institute, grid.419087.3
- (134) Broad Institute, grid.66859.34
- (135) Laval University, grid.23856.3a
- (136) Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK
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Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
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