A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2.

Song, H; Ramus, SJ; Tyrer, J; Bolton, KL; Gentry-Maharaj, A; Wozniak, E; Anton-Culver, H; Chang-Claude, J; Cramer, DW; DiCioccio, R; Dörk, T; Goode, EL; Goodman, MT; Schildkraut, JM; Sellers, T; Baglietto, L; Beckmann, MW; Beesley, J; Blaakaer, J; Carney, ME; Chanock, S; Chen, Z; Cunningham, JM; Dicks, E; Doherty, JA; Dürst, M; Ekici, AB; Fenstermacher, D; Fridley, BL; Giles, G; Gore, ME; De Vivo, I; Hillemanns, P; Hogdall, C; Hogdall, E; Iversen, ES; Jacobs, IJ; Jakubowska, A; Li, D; Lissowska, J; Lubi?ski, J; Lurie, G; McGuire, V; McLaughlin, J; Medrek, K; Moorman, PG; Moysich, K; Narod, S; Phelan, C; Pye, C; Risch, H; Runnebaum, IB; Severi, G; Southey, M; Stram, DO; Thiel, FC; Terry, KL; Tsai, YY; Tworoger, SS; Van Den Berg, DJ; Vierkant, RA; Wang-Gohrke, S; Webb, PM; Wilkens, LR; Wu, AH; Yang, H; Brewster, W; Ziogas, A; Australian Cancer (Ovarian) Study, ; Australian Ovarian Cancer Study Group, ; Ovarian Cancer Association Consortium, ; Houlston, R; Tomlinson, I; Whittemore, AS; Rossing, MA; Ponder, BA; Pearce, CL; Ness, RB; Menon, U; Kjaer, SK; Gronwald, J; Garcia-Closas, M; Fasching, PA; Easton, DF; Chenevix-Trench, G; Berchuck, A; Pharoah, PD; Gayther, SA; (2009) A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature genetics, 41 (9). pp. 996-1000. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.424

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Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 19648919
Web of Science ID: 269382100011
URI: http://researchonline.lshtm.ac.uk/id/eprint/2450


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