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


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).

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Figure 1: Genotype-specific risks of SNP rs3814113 for ovarian cancer by stage and by study.
Figure 2: Map of associated regions on 9p22.2 (nucleotides 16655021–17155021).


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We thank all the individuals who took part in this study. We thank all the researchers, clinicians and administrative staff who have enabled the many studies contributing to this work. In particular we thank A. Ryan and J. Ford (UKOPS); J. Morrison, the SEARCH team, U. Eilber and T. Koehler (GER); D. Bowtell, A. deFazio, D. Gertig, A. Green (AOCS); A. Green, P. Parsons, N. Hayward, D. Whiteman (ACS); L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao, M. Stagner (POL1); N. Bogdanova, S. Haubold, P. Schürmann, F. Kramer, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJOCS). The genotyping and data analysis for this study was supported by a project grant from Cancer Research UK. We acknowledge the computational resources provided by the University of Cambridge (CamGrid). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith. D.F.E. and P.D.P.P. are supported by Cancer Research UK, S.J.R. by the Mermaid/Eve Appeal, G.C.-T. and P.M.W. by the NHMRC, and P.A.F. by the Deutsche Krebshilfe e.V. Funding of the constituent studies was provided by the Roswell Park Alliance, the Danish Cancer Society and the US National Cancer Institute (CA71766, CA16056, R01 CA61107, R01 CA122443, R01 CA054419, P50 CA105009,R01CA114343, R01 CA87538, R01 CA112523, R01-CA- 58598, N01-CN-55424 and N01-PC-35137, R01-CA-122443, CA-58860, CA-92044), the US Army Medical Research and Material Command (DAMD17-01-1-0729), the Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study), the National Health and Medical Research Council of Australia (199600; ACS study), German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401), and the genotyping in part by the state of Baden-Württemberg through Medical Faculty of the University of Ulm (P.685; GER), the Mayo Foundation and the Lon V. Smith Foundation (grant LVS-39420). The UKOPS study is funded by the Oak Foundation. Some of this work was undertaken at University College Hospital, London which receives a proportion of its funding from the UK Department of Health's National Institute for Health Research Biomedical Research Centre funding scheme.

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P.D.P.P., S.A.G. and D.F.E. designed the study and obtained financial support. J.T. and H.S. conducted the statistical analysis. S.A.G., S.J.R., H.S. and P.D.P.P. coordinated the studies used in stage 1 and stage 2. H.S. designed and coordinated the stage 3 experiment. The remaining authors coordinated the studies in stage 2 or undertook genotyping in stage 3. H.S., S.J.R. and S.A.G. drafted the manuscript, with substantial input from J.T. and P.D.P.P. All authors contributed to the final draft.

Corresponding author

Correspondence to Paul D P Pharoah.

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Song, H., Ramus, S., Tyrer, J. et al. A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet 41, 996–1000 (2009).

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