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Sep 20, 2010

Investigators Identify Risk Loci for Ovarian Cancer

  • A consortium of researchers has identified chromosome locations with genetic changes that are likely to alter a woman's risk of developing ovarian cancer. Two separate genome-wide association studies confirmed two loci and found three additional loci with genome-wide significance.

    To identify common low-penetrance ovarian cancer susceptibility genes, a group of investigators conducted a genome-wide association study of 507,094 SNPs in 1,768 ovarian cancer patients and 2,354 controls. A follow-up study of 21,955 SNPs in 4,162 cases and 4,810 controls was also conducted. Results appear in a paper titled “A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24” in Nature Genetics.

    The researchers identified a confirmed susceptibility locus at 9p22 in the gene BNC2. They also found nine additional candidate loci that were discovered after stratifying cases by histology. These were genotyped in an additional 4,353 cases and 6,021 controls.

    The scientists confirmed two new susceptibility loci, 8q24 and 2q31, and pinpointed two loci that approached genome-wide significance, 3q25 and 17q21. The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP, and SKAP1 genes at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development, the team concludes.

    Details of the second study, conducted by the same research team, appear in a paper titled “Common variants at 19p13 are associated with susceptibility to ovarian cancer.” The investigators performed a three-phase genome-wide association study of epithelial ovarian cancer survival in 8,951 (epithelial ovarian cancer) EOC patients with available survival time data and a parallel association analysis of EOC susceptibility.

    Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival, but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC. Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.


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