Association of RAD51C germline mutations with breast cancer among Bahamians.

Abstract

RAD51C is known as an ovarian cancer gene; however, its role in breast cancer susceptibility is less clear. As part of a larger study, we assessed the role of germline RAD51C mutations in breast cancer development. We studied 387 unselected, BRCA1- and BRCA2-negative, Bahamian breast cancer cases and 653 controls to search for novel genetic associations with breast cancer development. During the first phase of the study, whole exome sequencing was utilized in 96 cases to identify an association between novel genes and breast cancer susceptibility. In the second phase of the study, targeted gene sequencing was utilized in the entirety of the cases and controls to identify an association between novel genetic mutations and breast cancer development. A RAD51C mutation was found in five breast cancer cases and in no control (5/387 versus 0/653; p = 0.007). None of the mutation-positive cases reported a family history of ovarian cancer. These data support increasing evidence that RAD51C mutations contribute to breast cancer susceptibility, although the impact may vary substantially from country to country.