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

Eli Marie Grindedal; Manuela Zucknick; Sigrid Tronsli Hovland; Tom K Grimsrud; Lovise Mæhle

doi:10.1038/s44276-025-00199-2

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

BJC Rep. 2025 Dec 12;3(1):83. doi: 10.1038/s44276-025-00199-2.

Authors

Eli Marie Grindedal¹, Manuela Zucknick^{2

3}, Sigrid Tronsli Hovland⁴, Tom K Grimsrud⁵, Lovise Mæhle⁴

Affiliations

¹ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. eligr@ous-hf.no.
² Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
³ Oslo Centre for Biostatistics and Epidemiology, Research Support Service, Oslo University Hospital, Oslo, Norway.
⁴ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁵ Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.

Abstract

Background: BRCA1 and BRCA2 carriers have increased risk of pancreatic cancer (PC). We have studied prospective incidence rate and cumulative risk of PC in a large cohort of confirmed carriers.

Methods: BRCA1/2 carriers without 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 4.73 expected (SIR 2.75, 95% CI 1.46-4,70). In 1476 BRCA2 carriers, we observed 9 cases versus 1.89 expected (SIR 4.76, 95% CI 2.18-9.04). Suggestively, there were higher risks among female BRCA2 carriers (SIR 6.52, 95% CI 2.82-12.85, 8 cases) and male BRCA1 carriers (SIR 5.51, 95% CI 2.52-10.47, 9 cases), who had cumulative risks at 70 years of 1.2% and 2.5% respectively.

Conclusions: BRCA1/2 carriers had three times more cases of PC than expected, suggestively higher among female BRCA2 and male BRCA1 carriers. Cumulative risk of PC at 70 years in the latter two groups was less than 3% (0.5% and 0.7% in all Norwegian males and females observed until age 70 based on population data).

Abstract

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