RAD51 Mutations Linked With Moderate Ovarian Cancer Risk

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Deleterious mutations in RAD51C and RAD51D genes are associated with increased risk of epithelial ovarian cancer.
Deleterious mutations in RAD51C and RAD51D genes are associated with increased risk of epithelial ovarian cancer.

Deleterious mutations in RAD51C and RAD51D genes are associated with increased risk of epithelial ovarian cancer (EOC), according to a study published in the Journal of Clinical Oncology.

Honglin Song, Ph.D., from the University of Cambridge in the United Kingdom, and colleagues conducted a genetic study using germline DNA from 3,429 patients with invasive EOC and 2,772 controls from a case-control study, as well as 2,000 unaffected BRCA1/2-negative women from the UK Familial Ovarian Cancer Screening Study.

The coding sequence and splice site boundaries of the RAD51B, RAD51C, and RAD51D genes were sequenced and analyzed.

The researchers identified deleterious mutations in 0.82 percent of EOC cases and 0.11 percent of controls in the case-control study (P < 0.001).

In EOC cases, mutations were more frequent in RAD51C and RAD51D than in RAD51B carriers (0.41 and 0.35, respectively, versus 0.06 percent). The odds ratios associated with RAD51C and RAD51D mutations were 5.2 (P = 0.035) and 12 (P = 0.019), respectively.

RELATED: Multigene Testing Identifies More Mutations in Breast, Ovarian Cancer

The prevalence of RAD51 mutations was 0.65 percent in unaffected UK FCOSS participants, significantly higher than in controls (P < 0.01). RAD51 mutation carriers were more likely to have a family history of ovarian cancer than noncarriers (P < 0.001).

"These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing," the authors write.

Several authors disclosed financial ties to the pharmaceutical and biotechnology industries.

Reference

  1. Song H, Dicks E, Ramus SJ, et al. Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. Journal of Clinical Oncology. doi: 10.1200/JCO.2015.61.2408. [epub ahead of print]. August 10, 2015.

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