Literature DB >> 19648919

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

Honglin Song1, Susan J Ramus, Jonathan Tyrer, Kelly L Bolton, Aleksandra Gentry-Maharaj, Eva Wozniak, Hoda Anton-Culver, Jenny Chang-Claude, Daniel W Cramer, Richard DiCioccio, Thilo Dörk, Ellen L Goode, Marc T Goodman, Joellen M Schildkraut, Thomas Sellers, Laura Baglietto, Matthias W Beckmann, Jonathan Beesley, Jan Blaakaer, Michael E Carney, Stephen Chanock, Zhihua Chen, Julie M Cunningham, Ed Dicks, Jennifer A Doherty, Matthias Dürst, Arif B Ekici, David Fenstermacher, Brooke L Fridley, Graham Giles, Martin E Gore, Immaculata De Vivo, Peter Hillemanns, Claus Hogdall, Estrid Hogdall, Edwin S Iversen, Ian J Jacobs, Anna Jakubowska, Dong Li, Jolanta Lissowska, Jan Lubiński, Galina Lurie, Valerie McGuire, John McLaughlin, Krzysztof Medrek, Patricia G Moorman, Kirsten Moysich, Steven Narod, Catherine Phelan, Carole Pye, Harvey Risch, Ingo B Runnebaum, Gianluca Severi, Melissa Southey, Daniel O Stram, Falk C Thiel, Kathryn L Terry, Ya-Yu Tsai, Shelley S Tworoger, David J Van Den Berg, Robert A Vierkant, Shan Wang-Gohrke, Penelope M Webb, Lynne R Wilkens, Anna H Wu, Hannah Yang, Wendy Brewster, Argyrios Ziogas, Richard Houlston, Ian Tomlinson, Alice S Whittemore, Mary Anne Rossing, Bruce A J Ponder, Celeste Leigh Pearce, Roberta B Ness, Usha Menon, Susanne Krüger Kjaer, Jacek Gronwald, Montserrat Garcia-Closas, Peter A Fasching, Douglas F Easton, Georgia Chenevix-Trench, Andrew Berchuck, Paul D P Pharoah, Simon A Gayther.   

Abstract

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)).

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Year:  2009        PMID: 19648919      PMCID: PMC2844110          DOI: 10.1038/ng.424

Source DB:  PubMed          Journal:  Nat Genet        ISSN: 1061-4036            Impact factor:   38.330


  40 in total

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  162 in total

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