RAD51C-Related Cancer Risk
The RAD51C gene is classified as a “moderate risk” gene, meaning that there is a modestly increased risk for certain types of cancers. Multiple studies have demonstrated an association between RAD51C pathogenic gene mutations and a risk for ovarian cancer. Women who carry RAD51C pathogenic mutations are approximately 5 times more likely to develop ovarian cancer than women in the general population. Data regarding an association between RAD51C gene mutations and breast cancer risk have been inconsistent, but there does not appear to be an overall increased risk for breast cancer. Some studies suggest an association with triple negative breast cancer, but it is not clear that the risk is sufficient to change management recommendations. Further research is needed to understand the interactions of moderate risk genes and family history on lifetime cancer risk.
Rarely, an individual will inherit two RAD51C gene mutations – one from each parent. When this happens, the child has a severe disease called Fanconi Anemia (FA). Children who have FA have blood problems, developmental issues, and increased risk of cancers such as leukemia and lymphoma.
RAD51C cancer screening and risk-reducing options
The best long-term medical management for individuals who carry a mutation in the RAD51C gene is a topic of on-going research. Healthcare providers oftentimes rely on an individual’s personal and family history to guide medical care.
- Ovary: Depending upon personal and family history, women should discuss bilateral salpingo-oophorectomy (with or without hysterectomy) with their physicians between the ages of 45-50 years. There is no evidence that ovarian cancer screening with currently available methods (e.g. transvaginal ultrasound and CA-125 blood measurement) reduces ovarian cancer mortality.
- Breast: Women should pursue standard clinical breast exams and mammography. In the presence of a strong personal and/or family history of breast cancer, some women might also consider increased breast cancer surveillance with breast MRI.
RAD51C associated therapeutic/ treatment implications
Individuals who have a cancer diagnosis and an identified RAD51C pathogenic mutation should speak with their treating physician about the availability of targeted/ personalized treatment options.
Clinical trials evaluating different medications in individuals who have pathogenic mutations in RAD51C and/or other related genes might be available now or in the future.
RAD51C testing in other family members
At this point in time, testing adult family members for a moderate risk gene mutation does NOT provide the same clarity or guidance that testing for a high risk gene mutation does. This is because moderate risk gene mutations should not be assumed to be the sole explanation for a particular family’s history of cancer. For example, a family could have additional unidentified genetic and/or non-genetic risk factors contributing to the development of cancer seen in family members. It is recommended that family members discuss risks, benefits and limitations of genetic testing with their physician and/or genetic counselor. If an adult family member were to test positive for the familial RAD51C gene mutation, increased cancer screening might be considered. However, given the current lack of data regarding RAD51C gene mutations, if an adult family member were to test negative for a familial RAD51C gene mutation, that individual may still be at increased risk for cancer depending upon the family history and possibility for other genes to be playing a role. Cancer screening should be performed in accordance with the family history until further data is available.
As research and data on cancer risk estimates continue to evolve, physicians and researchers will gain a better understanding of how a RAD51C gene mutation influences medical care. Because the information provided to patients will almost certainly change, those with a RAD51C gene mutation are encouraged to keep in touch with their medical providers in order to receive updates.
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