학술논문
Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci
Document Type
article
Author
DeVries, Amber A; Dennis, Joe; Tyrer, Jonathan P; Peng, Pei-Chen; Coetzee, Simon G; Reyes, Alberto L; Plummer, Jasmine T; Davis, Brian D; Chen, Stephanie S; Dezem, Felipe Segato; Aben, Katja KH; Anton-Culver, Hoda; Antonenkova, Natalia N; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Berchuck, Andrew; Bogdanova, Natalia V; Bogdanova-Markov, Nadja; Brenton, James D; Butzow, Ralf; Campbell, Ian; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Cook, Linda S; DeFazio, Anna; Doherty, Jennifer A; Dörk, Thilo; Eccles, Diana M; Eliassen, A Heather; Fasching, Peter A; Fortner, Renée T; Giles, Graham G; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Webb, P; DeFazio, A; Friedlander, M; Obermair, A; Grant, P; Nagle, C; Beesley, V; Chevenix-Trench, G; Bowtell, D; Blomfield, P; Brand, A; Davis, A; Leung, Y; Nicklin, J; Quinn, M; Livingstone, K; O'Neill, H; Williams, M; Black, A; Hadley, A; Glasgow, A; Garrett, A; Rao, A; Shannon, C; Steer, C; Allen, D; Neesham, D; Otton, G; Au-Yeung, G; Goss, G; Wain, G; Gard, G; Robertson, G; Lombard, J; Tan, J; McNeilage, J; Power, J; Coward, J; Miller, J; Carter, J; Lamont, J; Wong, KM; Reid, K; Perrin, L; Milishkin, L; Nascimento, M; Buck, M; Bunting, M; Harrison, M; Chetty, N; Hacker, N; McNally, O; Harnett, P; Beale, P; Awad, R; Mohan, R; Farrell, R; McIntosh, R; Rome, R; Sayer, R; Houghton, R; Hogg, R; Land, R; Baron-Hay, S; Paramasivum, S
Source
Journal of the National Cancer Institute. 114(11)
Subject
Language
Abstract
BackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P