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Prostate cancer risk in male BRCA carriers in UK and Ireland

Men with BRCA mutations have a 27 per cent higher absolute risk for prostate cancer (PCa), data from the UK and Ireland show.

The prospective cohort study, published in European Urology, recruited 376 men carrying BRCA1 mutations and 447 carrying BRCA2 mutations from clinical genetics centres in the UK and Ireland.

It found that BRCA2 carriers had a standardised incidence/mortality ratios (SIRs/SMRs) of 4.45 (95% CI, 2.99-6.61) relative to population incidences or mortality rates and an absolute PCa risk of 27 per cent (95% CI, 17-41%) and 60 per cent (95% CI, 43-78%) by ages 75 and 85 years, respectively.

For BRCA1 carriers, overall SIR was 2.35 (95% CI, 1.43-3.88). The corresponding SIR at age <65 years was 3.57 (95% CI, 1.68-7.58). However, BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects.

BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI, 1.07-5.64) compared to population incidences, corresponding to lower PCa risk (HR, 0.37; 95% CI, 0.14-0.96) than for mutations outside the region.

PCa risk for BRCA2 carriers increased with family history (HR per affected relative, 1.68; 95% CI, 0.99-2.85). BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR, 5.07; 95% CI, 3.20-8.02) than Gleason score ≤6 PCa (SIR, 3.03; 95% CI, 1.24-7.44), and a higher risk of death from PCa (SMR, 3.85; 95% CI, 1.44-10.3).

“Depending on the assumptions, we found that BRCA2 carriers are at a two to five times higher risk of PCa compared to men in the general population,” the authors said. They say the results will be informative in the counselling of men who carry BRCA1 or BRCA2 mutations.


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