A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

Ovarian cancer (OC) accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance OC susceptibility genes, we conducted a genome-wide association study (GWAS) of 507,094 SNPs in 1,768 cases and 2,354 controls, with follow-up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (BNC2)1. Here, we report on nine additional candidate loci (p≤10-4), identified after stratifying cases by histology, genotyped in an additional 4,353 cases and 6,021 controls. Two novel susceptibility loci with p≤5×10-8 were confirmed (8q24, p=8.0×10-15 and 2q31, p=3.8×10-14); two additional loci were also identified that approached genome-wide significance (3q25, p=7.1×10-8 and 17q21, p=1.4×10-7). The associations with serous OC were generally stronger than other subtypes. Analysis of HOXD1, MYC, TiPARP, and SKAP1 at these loci, and BNC2 at 9p22, supports a functional role for these genes in OC development