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. 2009 Sep;41(9):996-1000.
doi: 10.1038/ng.424. Epub 2009 Aug 2.

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

Honglin Song  1 , 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; Australian Cancer (Ovarian) Study; Australian Ovarian Cancer Study Group; Ovarian Cancer Association Consortium; 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
Affiliations

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

Honglin Song et al. Nat Genet. 2009 Sep.

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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Figures

Figure 1
Figure 1
Genotype-specific risks of SNP rs3814113 for ovarian cancer by stage and by study - (a) all epithelial ovarian cancer cases, (b) serous ovarian cancer cases only. Results are based on analyses restricted to subjects of European ancestry.
Figure 2
Figure 2
Map of associated regions on 9p22.2 (nucl. 16655021-17155021). The top panel shows the LD blocks around rs3814113 (±250 kb) for SNPs with MAF≥ 0.05 based on Hapmap CEU data. Squares on the LD block indicate the correlation (r2) between SNPs on a greyscale (darker squares = higher correlations). Approximate location of BNC2 (nucl. 16860786-16399502), CNTLN (nucl. 17125038-17493915) and LOC648570 (nucl. 16777433-16775576) were inferred from the NCBI reference assembly (solid line). The lower panel shows the highlighted LD block in greater detail. The star indicates the location of the most strongly associated SNP rs3814113. The black circles show the position of the other 11 SNPs that reached genome wide significance. The numbers refer to the SNP identifiers in Supplementary Table 2.
See this image and copyright information in PMC

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