Two days ago, we discussed a recent study by Dr. Nazneen Rahman and colleagues which clearly demonstrated that inherited mutations in a gene called RAD51D result in a substantial elevation in risk for ovarian cancer. Some families with mutations in the study also had some other cancer types in the family tree. So, does this mean that the other cancer types in these families are also due to the RAD51D mutations?
In short, the answer is that we don't know. Ovarian cancer risk was the only one that Dr. Rahman and her colleagues could pin down as being associated with RAD51D mutations with any statistical confidence. For the others, future studies can address the specific question; however, they may be challenging and require extremely large sample sizes in order to have the statistical power to answer the question.
Here are the other cancer types that were seen in the eight families with inactivating RAD51D mutations in the study:
Breast Cancer
- Seen in 8 out of 8 families (not surprising given that the families were included in the study because they had both ovarian and breast cancer)
- There were 13 breast cancer cases total in these 8 families
- Two of the breast cancer cases were bilateral
- Seven of the 13 cases were found to have inactivating RAD51D mutations (the other 6 were not tested)
- In contrast to ovarian cancer, the association of RAD51D mutations with breast cancer was not statistically significant (Relative Risk = 1.32 with 95% confidence intervals from 0.59 - 2.96)
Colorectal Cancer
- Seen in 5 out of 8 families (keep in mind that some of these extended families are quite large and that colorectal cancer is common)
- There were 8 total colorectal cancer cases in the 5 families
- None of the affected individuals were tested for the presence of mutations in this study
Lung Cancer
- Seen in 1 individual in 1 out of 8 families (keep in mind that some of these extended families are quite large and that lung cancer is common)
- The individual with lung cancer was not tested for the presence of the familial RAD51D mutation in this study
Non-Hodgkin Lymphoma
- Seen in 1 individual in 1 out of 8 families
- The individual with NHL was not tested for the presence of the familial RAD51D mutation
Pancreatic Cancer
- Seen in 2 individuals total from 2 out of 8 families
- The 2 individuals with pancreatic cancer were not tested for the familial RAD51D mutation
Prostate Cancer
- A total of 2 cases were seen in 1 out of the 8 families
- The 2 individuals with prostate cancer were not tested for the familial RAD51D mutation
It's very important to keep in mind that seeing these cancers in these families could just be due to chance or to the fact that the families were more likely to come to the researchers' attention because of the other cancers (particularly breast cancer). Thus, we can't say anything about whether RAD51D mutations may lead to elevated risk for any cancer other than ovarian cancer based on this study. Nevertheless, it will be important in the future to keep an eye on this.
Bottom Line Implications
1. Mutations in the RAD51D gene lead to ovarian cancer risk in some families in which the familial ovarian cancer risk is not explained by mutations in BRCA1/2
2. Although several other cancer types (including breast cancer) were seen in the families with mutations, there was no statistically significant evidence from this study implicating RAD51D mutations in risk for any of the other cancer types.
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Selected References
Loveday C, Turnbull C, Ramsay E, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nature Genetics 2011 (Published online August 7 2011)
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