Germline BRCA1 mutations increase prostate cancer risk
British Journal of Cancer, 05/04/2012
Leongamornlert D et al. – This study shows evidence for an increased risk of PrCa in men who harbour germline mutations in BRCA1. This could have a significant impact on possible screening strategies and targeted treatments.Methods
- We screened 913 cases aged 36–86 years for germline BRCA1 mutation, with the study enriched for cases with an early age of onset.
- We analysed the entire coding region of the BRCA1 gene using Sanger sequencing.
- Multiplex ligation-dependent probe amplification was also used to assess the frequency of large rearrangements in 460 cases.
- We identified 4 deleterious mutations and 45 unclassified variants (UV).
- The frequency of deleterious BRCA1 mutation in this study is 0.45%; three of the mutation carriers were affected at age 65 years and one developed PrCa at 69 years.
- Using previously estimated population carrier frequencies, deleterious BRCA1 mutations confer a relative risk of PrCa of ~3.75-fold, (95% confidence interval 1.02–9.6) translating to a 8.6% cumulative risk by age 65.