Article
Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA
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- (1) BC Cancer Agency, grid.248762.d
- (2) Alberta Health Services, grid.413574.0
- (3) University of Calgary, grid.22072.35
- (4) Moffitt Cancer Center, grid.468198.a
- (5) University of British Columbia, grid.17091.3e
- (6) QIMR Berghofer Medical Research Institute, grid.1049.c
- (7) Peter MacCallum Cancer Centre, grid.1055.1
- (8) Department of Gynecology and Obstetrics, Comprehensive Cancer Center, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
- (9) University of Erlangen-Nuremberg, grid.5330.5
- (10) University of California, Los Angeles, grid.19006.3e
- (11) Flanders Institute for Biotechnology, grid.11486.3a
- (12) KU Leuven, grid.5596.f
- (13) Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Louvain, Belgium
- (14) Dartmouth College, grid.254880.3
- (15) Fred Hutchinson Cancer Research Center, grid.270240.3
- (16) University of Washington, grid.34477.33
- (17) German Cancer Research Center, grid.7497.d
- (18) Roswell Park Cancer Institute, grid.240614.5
- (19) University of Hawaii at Manoa, grid.410445.0
- (20) Cedars-Sinai Medical Center, grid.50956.3f
- (21) Department of Obstetrics and Gynaecology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany
- (22) Hannover Medical School, grid.10423.34
- (23) Aleksandrov Byelorussian Institute for Oncology and Medical Radiology, Minsk, Belarus
- (24) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
- (25) Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
- (26) University of Pittsburgh, grid.21925.3d
- (27) Women’s Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
- (28) The University of Texas Health Science Center at Houston, grid.267308.8
- (29) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
- (30) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
- (31) Institut für Humangenetik, Wiesbaden, Germany
- (32) Danish Cancer Society, grid.417390.8
- (33) Rigshospitalet, grid.475435.4, Capital Region
- (34) University of Copenhagen, grid.5254.6, KU
- (35) University of Kansas Medical Center, grid.412016.0
- (36) Mayo Clinic, grid.66875.3a
- (37) Cancer Council Victoria, grid.3263.4
- (38) University of Melbourne, grid.1008.9
- (39) Texas Southern University, grid.264771.1
- (40) The University of Texas MD Anderson Cancer Center, grid.240145.6
- (41) Memorial Sloan Kettering Cancer Center, grid.51462.34
- (42) Duke University, grid.26009.3d
- (43) Duke University Hospital, grid.189509.c
- (44) Brigham and Women's Hospital, grid.62560.37
- (45) Harvard University, grid.38142.3c
- (46) Channing Division of Network Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
- (47) Rutgers, The State University of New Jersey, grid.430387.b
- (48) Haukeland University Hospital, grid.412008.f
- (49) University of Bergen, grid.7914.b
- (50) Radboud University Nijmegen Medical Centre, grid.10417.33
- (51) Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands
- (52) Oregon Health & Science University, grid.5288.7
- (53) Pomeranian Medical University, grid.107950.a
- (54) National Cancer Institute, grid.48336.3a
- (55) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
- (56) Breast Cancer Now, grid.458394.7
- (57) Institute of Cancer Research, grid.18886.3f
- (58) University of Cambridge, grid.5335.0
- (59) Faculty of Medicine, University Hospital Southampton, University of Southampton, Southampton, UK
- (60) Stanford University, grid.168010.e
- (61) Imperial College London, grid.7445.2
- (62) Beatson West of Scotland Cancer Centre, grid.422301.6
- (63) Yale University, grid.47100.32
- (64) Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
- (65) University of Toronto, grid.17063.33
- (66) University of California, Irvine, grid.266093.8
- (67) University College London, grid.83440.3b
- (68) University of Southern California, grid.42505.36
- (69) University of New Mexico, grid.266832.b
- (70) Simon Fraser University, grid.61971.38
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Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.
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