In this study, BRIP1, PALB2, and RAD51C were sequenced for mutations as a result of previously being associated with breast cancer risk due to their role in the double-strand break repair pathway and their close association with BRCA1 and BRCA2.
Large international collaborative studies are needed to quantify the relative risk of RAD51C alterations for BC and to unravel the genetic modifying factors that determine phenotypic variability with respect to cancer site.
Our results support that RAD51C is a rare breast and ovarian cancer susceptibility gene and may contribute to a small fraction of families including breast and ovarian cancer cases and families with only breast cancer.
In the Finnish population, we have identified two founder mutations in RAD51C that increase the risk of ovarian cancer but not breast cancer in the absence of ovarian cancer.
Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer.
Consistent with published results from similar follow-up studies, we suggest that RAD51C mutations are rare events among high-risk breast cancer and breast/ovarian cancer families.
Our data confirm a consistent but low frequency (2/335 families) of inactivating RAD51C mutations among families with a history of both breast and ovarian cancer and an absence of mutations among breast cancer only families (0/1,053 families).