Prostate cancer risk by BRCA2 genomic regions

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3’) wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared to population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.58) and were at higher risk of PCa than carriers of other BRCA2 PVs (SIR=3.31, 95% CI 1.97-5.57; hazard ratio [HR]=2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23%-72%) by age 75 and 78% (95% CI 54%-94%) by age 85. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort.