Inherited Gene Mutation Leads to Ovarian Cancer

Women who carry an inherited fault in a certain gene are more than three times more likely to develop epithelial ovarian cancer (EOC) than those without the mutation.

Risk prediction based on identifying germline mutations in ovarian cancer susceptibility genes could have a clinically significant impact on reducing disease mortality as around 18 women in every 1,000 develop ovarian cancer, but this risk increases to around 58 women in every 1,000 for women with a mutation in a specific gene.


An international team of scientists led by those at the University of Cambridge Cancer Group (UK) compared the genes of more than 8,000 white European women which included around 3,250 women diagnosed with ovarian cancer, 3,400 women who did not have cancer and 2,000 women who had a family history of the disease. For each gene, they estimated the prevalence and EOC risks and evaluated associations between germline variant status and clinical and epidemiological risk factor information.

Next generation sequencing was used to identify germline mutations in the coding regions of four candidate susceptibility genes: BRCA1 Interacting Protein C-Terminal Helicase 1 (BRIP1), BRCA1 Associated RING Domain 1 (BARD1), Partner and Localizer of BRCA2 (PALB2) and Nibrin (NBN). The scientists found an increased frequency of deleterious mutations in BRIP1 in case patients (0.9%) and in the participants from a clinical screening trial of ovarian cancer (UKFOCSS) (0.6%) compared with control patients (0.09%), but no differences for BARD1, NBN1 or PALB2.

The authors concluded that deleterious germline mutations in BRIP1 are associated with a moderate increase in EOC risk. These data have clinical implications for risk prediction and prevention approaches for ovarian cancer and emphasize the critical need for risk estimates based on very large sample sizes before genes of moderate penetrance have clinical utility in cancer prevention.

Paul D. P. Pharoah, MD, a professor of Cancer Epidemiology and co-director of the study, said, “Our work has found a valuable piece of the puzzle behind ovarian cancer and we hope that our work could eventually form the basis of a genetic test to identify women at greatest risk. Finding these women will help us prevent more cancers and save lives. This would be important in a disease like ovarian cancer, which tends to be diagnosed at a late stage when the chances of survival are worse.” The study was published in the January 2016 edition of the Journal of the National Cancer Institute.

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University of Cambridge Cancer Group