Prospective Implications of BRCA Mutations in Prostate Cancer
Posted: Monday, December 23, 2019
A new prospective study provides further support of the association between BRCA mutations and patterns of prostate cancer risk, especially in aggressive prostate disease. Antonis C. Antoniou, PhD, of the University of Cambridge, published the work he completed along with colleagues in European Urology.
“The results substantiate prostate cancer risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive prostate cancer, and give some support for a weaker association in BRCA1 carriers,” the investigators concluded.
This study followed two cohorts of men unaffected by prostate cancer who were identified from clinical genetics centers in the United Kingdom and Ireland. One group consisted of 376 men with BRCA1 mutations, and the other was composed of 447 men with BRCA2 mutations. The BRCA1 group was followed for a median of 5.9 years, and the BRCA2 group was followed for a median of 5.3 years.
By the end of follow-up, 16 BRCA1 carriers and 26 BRCA2 carriers were diagnosed with prostate cancer. The standardized incidence ratio for BRCA2 carriers was 4.45, and the absolute prostate cancer risk for these patients was 27% and 60% by ages 75 and 85, respectively. In contrast, BRCA1 carriers had a standardized incidence ratio of 2.35, but this value varied between 0.84 and 2.83 in sensitivity analyses. Risk for patients with BRCA2 mutations increased if they had a family history of prostate cancer, carrying a hazard ratio of 1.68 per affected relative. Additionally, BRCA2 carriers had a stronger association with a Gleason score over 7 (standardized incidence ratio = 5.07) than a Gleason score of 6 or less (standardized incidence ratio = 3.03). Patients with this mutation also had a higher risk of death from prostate cancer (standardized mortality ratio = 3.85).
Disclosure: The study authors reported no conflicts of interest.