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

Journal article

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)).

Authors: Song, H; Ramus, S; Tyrer, J; Bolton, K; Gentry-Maharaj, A

• Publication status: Published
• Journal: Nature genetics
• Volume: 41
• Issue: 9
• Pages: 996-1000
• Publication date: 2009-09-01
• DOI: 10.1038/ng.424
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Genome-Wide Association Study; Australian Cancer (Ovarian) Study; Odds Ratio; Alleles; Chromosomes, Human, Pair 9; Risk Factors; Molecular Sequence Data; Case-Control Studies; Ovarian Cancer Association Consortium; Confidence Intervals; Female; Linkage Disequilibrium; Gene Frequency; Haplotypes; Australian Ovarian Cancer Study Group; Polymorphism, Single Nucleotide; European Continental Ancestry Group; Australia; United States; Europe; Chromosome Mapping; Heterozygote; Humans; Ovarian Neoplasms; Genetic Predisposition to Disease; Base Sequence; Homozygote; Genotype