A prospective observational study of pancreatic cancer risk in men and women with pathogenic variants in BRCA1 or BRCA2

Background: BRCA1 and BRCA2 carriers have increased risk of pancreatic cancer (PC). We explored incidence rate and cumulative risk of PC in a large prospective cohort of confirmed carriers. Methods: BRCA1/2 carrierswithout PC prior to genetic testing were identified from the clinical registry at Section for Hereditary Cancer, Oslo University Hospital. Cancer diagnoses were collected from Cancer Registry of Norway (CRN). Standardized incidence ratios (SIRs) were derived from national reference rates. The Kaplan-Meier method was used to calculate cumulative risk. Results: Among 2681 BRCA1 carriers, we observed 13 cases versus 4.7 expected (SIR 2.8, 95% CI 2.1-5.0). In 1476 BRCA2 carriers, we observed 9 cases versus 1.9 expected (SIR 4.8, 95% CI 2.2–9.0). The highest risk was observed for female BRCA2 carriers (SIR 6.5, 95% CI 2.8–12.9, 8 cases) and male BRCA1 carriers (SIR 5.5, 95% CI 2.5–10.5, 9 cases), who had a cumulative risk at 70 years of 1.2% and 2.5% respectively. Conclusions: BRCA1/2 carriers had three times more cases of PC than expected, but a statistically significant increased incidence was only observed for female BRCA2 and male BRCA1 carriers. Cumulative risk of PC at 70 years in these two groups was less than 3%.