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GWAS META-ANALYSIS AND REPLICATION IDENTIFIES THREE NEW SUSCEPTIBILITY LOCI FOR OVARIAN CANCER
A meta-analysis (a re-analysis of other datasets) of earlier GWAS studies in ovarian cancer was conducted using a new genotyping platform called ‘iCOGS’, customized for the study of cancer. The iCOGS array which included 2,500 previously identified top candidates from ovarian cancer identified 2 previously identified associations at 3q25 and 17q21. In addition we identified 3 new loci, 2 at 8q21 near the MYC oncogene and 1 at 10p12. We also identified a serous specific association at 17q12, and proposed the CHMP4C gene as a candidate based on epigenomics signatures.
Abstract
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
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