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

2009; Nature Portfolio; Volume: 41; Issue: 9 Linguagem: Inglês

10.1038/ng.424

1546-1718

Honglin Song, Susan J. Ramus, Jonathan P. Tyrer, Kelly L. Bolton, Aleksandra Gentry‐Maharaj, Eva Wozniak, Hoda Anton‐Culver, Jenny Chang‐Claude, Daniel W. Cramer, Richard A. DiCioccio, Thilo Dörk, Ellen L. Goode, Marc T. Goodman, Joellen M. Schildkraut, Thomas A. Sellers, Laura Baglietto, Matthias W. Beckmann, Jonathan Beesley, Jan Blaakær, Michael E. Carney, Stephen J. Chanock, Zhihua Chen, Julie M. Cunningham, Ed Dicks, Jennifer A. Doherty, Matthias Dürst, Arif B. Ekici, David Fenstermacher, Brooke L. Fridley, Graham G. Giles, Martin Gore, Immaculata De Vivo, Peter Hillemanns, Claus Høgdall, Estrid Høgdall, Edwin S. Iversen, Ian Jacobs, Anna Jakubowska, Dong Li, Jolanta Lissowska, Jan Lubiński, Galina Lurie, Valerie McGuire, Esther M. John, Krzysztof Mędrek, Patricia G. Moorman, Kirsten B. Moysich, Steven A. Narod, Catherine Phelan, Carole Pye, Harvey A. Risch, Ingo B. Runnebaum, Gianluca Severi, Melissa C. 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 R. Brewster, Argyrios Ziogas, Richard S. Houlston, Ian Tomlinson, Alice S. Whittemore, Mary Anne Rossing, Bruce A.J. Ponder, Celeste Leigh Pearce, Roberta B. Ness, Usha Menon, Susanne K. Kjær, Jacek Gronwald, Montserrat García‐Closas, Peter A. Fasching, Douglas F. Easton, Georgia Chenevix‐Trench, Andrew Berchuck, Paul D.P. Pharoah, Simon A. Gayther,

BRCA gene mutations in cancer

Paul Pharoah and colleagues report results of the first genome-wide association study for epithelial ovarian cancer. They identify a susceptibility locus on chromosome 9p22. Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk1. 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 ∼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 × 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, Ptrend = 5.1 × 10−19). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73–0.81, Ptrend = 4.1 × 10−21).