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

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

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 ca...

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Veröffentlicht in:JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 2022-11, Vol.114 (11), p.1533-1544
Hauptverfasser: 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 K.H, Anton-Culver, Hoda, Antonenkova, Natalia N, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Berchuck, Andrew, Bogdanova, Natalia, Bogdanova-Markov, Nadja, Brenton, James D, Butzow, Ralf, Campbell, Ian, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Dork, Thilo, Eccles, Diana M, Eliassen, A. Heather, Fasching, Peter A, Fortner, Renee T, Giles, Graham G, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Hakansson, Niclas, Hildebrandt, Michelle A.T, Huff, Chad, Huntsman, David G, Jensen, Allan, Kar, Siddhartha, Karlan, Beth Y, Khusnutdinova, Elza K, Kiemeney, Lambertus A, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Labrie, Marilyne, Lambrechts, Diether, Le, Nhu D, Lubinski, Jan, May, Taymaa, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Monteiro, Alvaro N, Moysich, Kirsten B, Odunsi, Kunle, Olsson, Hakan, Pearce, Celeste L, Pejovic, Tanja, Ramus, Susan J, Riboli, Elio, Riggan, Marjorie J, Romieu, Isabelle, Sandler, Dale P, Schildkraut, Joellen M, Setiawan, V. Wendy, Sieh, Weiva, Song, Honglin, Sutphen, Rebecca, Terry, Kathryn L, Thompson, Pamela J, Titus, Linda, Tworoger, Shelley S, Van Nieuwenhuysen, Els, Edwards, Digna Velez, Webb, Penelope M, Wentzensen, Nicolas, Whittemore, Alice S, Wolk, Alicja, Wu, Anna H, Ziogas, Argyrios, Freedman, Matthew L, Lawrenson, Kate, Pharoah, Paul D.P, Easton, Douglas F, Gayther, Simon A, Jones, Michelle R
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Zusammenfassung: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 
ISSN:0027-8874