Routine Clinical Genetic Testing Should Include RAD51C, RAD51D, Study Suggests

RAD51C and RAD51D are moderate ovarian cancer susceptibility genes, a new study published online ahead of print this week in the Journal of Clinical Oncology has shown.

For the study, researchers sought to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to the risk of invasive epithelial ovarian cancer in the population and in high-risk individual who participated in a screening trial.

Using a case-control study of 3,429 patients with invasive epithelial ovarian cancer and 2,772 controls, researchers identified predicted deleterious mutations in 0.82% of ovarian cancer cases compared with 0.11% of controls (P<0.001).

Results showed that patients with RAD51C and RAD51D mutations were 5.2 and 12 times, respectively, more likely to develop ovarian cancer than the controls.

Researchers also assessed 2,000 unaffected women who wereBRCA1/2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS). They found that 0.65% of participants had RAD51 mutations, of which seven were RAD51C and 5 were RAD51D.

The study also demonstrated that RAD51 mutation carriers were more likely to have a family history of ovarian cancer compared with noncarriers of the gene mutations (P<0.001).

The findings suggest that RAD51C and RAD51D confer levels of risk of invasive epithelial ovarian cancer “that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing,” the authors wrote.

Reference

1. Song H, Dicks E, Tyrer JP, et al. Contribution of germline mutations in the RAD51B, RAD51C, and RAD51D genes to ovarian cancer in the population. J Clin Oncol. 2015. [epub ahead of print]. doi: 10.1200/JCO.2015.61.2408.