Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci.

Abstract:: BACKGROUND: Known 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. METHODS: Single 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. RESULTS: We 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

Authors:: AA DeVries, J Dennis, JP Tyrer, P-C Peng, SG Coetzee, AL Reyes, JT Plummer, BD Davis, SS Chen, FS Dezem, KKH Aben, H Anton-Culver, NN Antonenkova, MW Beckmann, A Beeghly-Fadiel, A Berchuck, NV Bogdanova, N Bogdanova-Markov, JD Brenton, R Butzow, I Campbell, J Chang-Claude, G Chenevix-Trench, LS Cook, A DeFazio, JA Doherty, T Dörk, DM Eccles, AH Eliassen, PA Fasching, RT Fortner, GG Giles, EL Goode, MT Goodman, J Gronwald, OPAL Study Group, AOCS Group, N Håkansson, MAT Hildebrandt, C Huff, DG Huntsman, A Jensen, S Kar, BY Karlan, EK Khusnutdinova, LA Kiemeney, SK Kjaer, J Kupryjanczyk, M Labrie, D Lambrechts, ND Le, J Lubiński, T May, U Menon, RL Milne, F Modugno, AN Monteiro, KB Moysich, K Odunsi, H Olsson, CL Pearce, T Pejovic, SJ Ramus, E Riboli, MJ Riggan, I Romieu, DP Sandler, JM Schildkraut, VW Setiawan, W Sieh, H Song, R Sutphen, KL Terry, PJ Thompson, L Titus, SS Tworoger, E Van Nieuwenhuysen, DV Edwards, PM Webb, N Wentzensen, AS Whittemore, A Wolk, AH Wu, A Ziogas, ML Freedman, K Lawrenson, PDP Pharoah, DF Easton, SA Gayther, MR Jones

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