Abstract
Pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are associated with an increased lifetime risk of pancreatic ductal adenocarcinoma (PDAC), and more recently have been associated with increased risk of biliary tract cancers (BTC). This study assessed the prevalence, age and gender distribution of PDAC/BTC cases in families known to carry a BRCA1/2 PV compared to those of the Irish population. A review of all families referred to a national genetics clinic from 09/11/1997 to 01/06/2018 was performed. The BOADICEA algorithm was used to estimate the probability that an untested relative of a known BRCA1/2 PV carrier with PDAC was a carrier. We reviewed 3252 family pedigrees, 1193 contained a proband who underwent testing for BRCA1/2 based on Manchester score ≥ 15. Among 128 BRCA2 PV-positive families, 27 (21%) contained a 1st/2nd/3rd-degree relative with PDAC, while of 116 BRCA1 PV-positive families, 11 (9%) contained a 1st/2nd/3rd-degree relative with PDAC. Within these 38 families, 25 patients with PDAC had ≥ 50% likelihood of being a BRCA1/2 PV carrier. This cohort had a median age at diagnosis of 55 years (range 33–75), with a mean (55 years) lower than 8364 patients with PDAC identified through the National Cancer Registry of Ireland (71 years, p < 0.0001). Six BRCA2 positive (5%) and 2 BRCA1 positive pedigrees (2%) included an individual with BTC; median age at diagnosis was 65 years (range 33–99). PDAC and BTC are prevalent in Irish families harbouring a BRCA2 PV and are associated with early-onset malignancy. This supports current guidelines recommending universal germline testing for PDAC patients.
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Acknowledgements
We are grateful to Sandra Deady, and other staff of the Irish National Cancer Registry for providing data on pancreaticobiliary cancer diagnoses in Ireland from 1997 to 2015.
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This work was supported by the Laidlaw Foundation, through the Laidlaw Research and Leadership programme.
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ML reports a Consulting/Advisory Role for Agios, Celgene, and Roche/Genentech. DG has received research funding from Roche, AstraZeneca and Pfizer, educational support from Roche, Pfizer, Bayer and AstraZeneca, and has worked in an advisory capacity for Roche, Pfizer, AstraZeneca, and Merck. KC reports institutional research funding from AstraZeneca, Syndax Pharmaceuticals and has worked in an advisory capacity for Tesaro, AstraZeneca, Onc Live, and MJH Life Sciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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This research was approved by the St James’s Hospital Research Ethics Committee and was performed in accordance with the Helsinki Declaration of 1975, as revised in 2000.
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Power, R., Leavy, C., Nolan, C. et al. Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants. Familial Cancer 20, 97–101 (2021). https://doi.org/10.1007/s10689-020-00205-1
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DOI: https://doi.org/10.1007/s10689-020-00205-1