Risks of non-breast, non-ovarian cancers for BRCA1 and BRCA2 pathogenic variant carriers: a prospective cohort study.
Level 3 - non-randomized controlled study
Prospective cohort study comparing cancer incidence in pathogenic variant carriers to population rates
PubMed 41776557 · doi:10.1186/s12916-026-04753-8
What was done
Prospective cohort study evaluating 1,260 BRCA1 and 1,058 BRCA2 pathogenic variant carriers (91% female; median baseline age 45.5 years) recruited from the BCFR and kConFab-FUS consortia. Participants were free of cancers other than breast or ovarian cancer at enrollment. Standardized incidence ratios (SIRs) relative to population rates, probability of relative risk exceeding 2, and cumulative risks to age 80 years were estimated across 16 non-breast, non-ovarian cancer types over a median follow-up of 11.4 years.
What was found
Across follow-up, 161 non-breast, non-ovarian cancers were recorded. In BRCA1 carriers, no statistically significant elevations were observed: prostate cancer SIR was 1.7 (95% CI 0.7–4.2; probability RR > 2 = 0%), pancreatic cancer SIR was 1.1 (95% CI 0.3–4.6; probability RR > 2 = 67%), and all non-pancreatic cancers combined SIR was 0.85 (95% CI 0.68–1.06). In BRCA2 carriers, significantly increased risks were observed for pancreatic cancer (SIR 6.6, 95% CI 3.8–11.6; cumulative risk to age 80: 8.3%), prostate cancer (SIR 3.6, 95% CI 1.9–6.8; cumulative risk to age 80: 82.0%), and stomach cancer (SIR 3.1, 95% CI 1.01–9.8; cumulative risk to age 80: 1.6%). The SIR for all other non-breast, non-ovarian cancers combined in BRCA2 carriers was 0.85 (95% CI 0.66–1.10).
Why it matters
This study provides prospective evidence refining non-breast and non-ovarian cancer risks in BRCA carriers, showing that elevated risks for pancreatic, prostate, and stomach cancers are largely restricted to BRCA2 carriers rather than BRCA1.
Limits
The study population was 91% female, which substantially limits precision for male-specific outcomes like prostate cancer despite large relative risk estimates. Low absolute event counts for individual rare cancer sites resulted in wide confidence intervals, and the cohort permitted individuals with prior breast or ovarian cancer at baseline.
Cited by
- supports Men carrying BRCA gene mutations have a higher risk of prostate cancer and other forms of cancer.