Background: Germline mutations in the BRCA2 gene have been suggested to account for about 5% of familial prostate cancer; mutations have been reported in 2% of early onset (i.e., </= 55 years) prostate cancer cases and a segregating founder mutation has been identified in Iceland (999del5). However, the role of BRCA2 in high risk prostate cancer pedigrees remains unclear.
Findings: We examined the potential involvement of BRCA2 in a set offive high-risk prostate cancer pedigrees in which all prostate cases were no more distantly related than two meioses from another case, and the resulting cluster contained at least four prostate cancer cases. We selected these five pedigrees from a larger dataset of 59 high-risk prostate cancer pedigrees analyzed in a genome-wide linkage screen. Selected pedigrees showed at least nominal linkage evidence to the BRCA2 region on chromosome 13q. We mutation screened all coding regions and intron/exon boundaries of the BRCA2 gene in the youngest prostate cancer case who carried the linked 13q segregating haplotype, as well as in a distantly related haplotype carrier to confirm any segregation. We observed no known protein truncating BRCA2 deleterious mutations. We identified one non-segregating BRCA2 variant of uncertain significance, one non-segregating intronic variant not previously reported, and a number of polymorphisms.
Conclusion: In this set of high-risk prostate cancer pedigrees with at least nominal linkage evidence to BRCA2, we saw no evidence for segregating BRCA2 protein truncating mutations in heritable prostate cancer.