Risk of Pancreatic Cancer Associated With Precursor Lesions in Individuals and First-Degree Relatives: A Nationwide...

The aim of this study was to evaluate the risk of pancreatic cancer in individuals with pathologically confirmed precursor lesions-including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, and mucinous cystic neoplasia-and their first-degree relatives.

Using nationwide population-based cohort study, we included all histopathologically diagnosed pancreatic precursors during 1981 to 2017 and up to 5 matched general population references in Sweden, and their first-degree relatives. Participants were followed through January 1st, 2020. Incidence rates and 95% confidence intervals were computed with the Poisson model, and hazard ratios were calculated using Cox proportional hazards regression.

We identified 3980 index participants (681 precursor patients and 3299 reference individuals) and 25,986 first-degree relatives. Twenty-four index participants and 136 first-degree relatives developed pancreatic cancer during follow-up. Compared with reference individuals, precursor patients had a 7.25-fold (95% confidence interval, 2.13-24.71) higher risk of pancreatic cancer, corresponding to 330 per 100,000 person-years (95% confidence interval, 191-568) in precursors vs 40 per 100,000 person-years (95% confidence interval, 22-71) in reference individuals, with a particularly high incidence of pancreatic cancer in participants with pancreatic intraepithelial neoplasia (785 per 100,000 person-years; 95% confidence interval, 446-1382). Compared with first-degree relatives of reference individuals, first-degree relatives of precursor patients had a hazard ratio of 2.59 (95% confidence interval, 1.71-3.91) for pancreatic cancer, and a hazard ratio of 15.94 (95% confidence interval, 3.04-83.69) for early-onset pancreatic cancer (aged <50 years). Pancreatic cancer risks in first-degree relatives were similar across precursor subtypes in index participants.

A substantially higher risk of pancreatic cancer in pathologically confirmed precursor patients and their first-degree relatives were observed. A family history of these lesions may be important in individual risk assessment of pancreatic cancer.