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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) surveillance is recommended for high-risk individuals (HRI) carrying pathogenic variants (PV) in PDAC susceptibility genes or meeting criteria for familial pancreatic cancer (FPC). Cigarette smoking drives earlier PDAC onset in general populations, but this effect is not well-characterized among HRIs. We hypothesized that smoking accelerates the age at PDAC diagnosis for HRIs. METHODS: We identified PDAC patients enrolled in the Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) study at the University of Pittsburgh who underwent multi-gene panel testing. Chi-square tests, t-tests, and analysis of variance were used to assess relationships between smoking history and PDAC diagnosis age. RESULTS: Of 3,602 patients with PDAC, 1,266 met eligibility criteria. 148 carried PVs in PDAC susceptibility genes, 154 had FPC, and 964 had sporadic PDAC. Among PV carriers, current smokers were diagnosed 4.1 years earlier than never smokers (P = 0.16). Compared to sporadic patients, PV carriers were diagnosed 1.6 years earlier (P = 0.55) among current smokers, 3.4 years earlier (P = 0.07) among past smokers, and 3.8 years earlier (P = 0.01) among never smokers. PV carriers who had quit smoking more than 10 years prior were diagnosed 9.0 years later than current smokers (P = 0.01) while those who had quit smoking within 10 years had no significant difference in diagnosis age. CONCLUSIONS: Cigarette smoking is associated with earlier development of PDAC among PV carriers, but smoking cessation of 10 years or more mitigates this effect. If confirmed in larger studies, these findings suggest smoking history should factor into the age at which PDAC surveillance begins.
Shu et al. (Fri,) studied this question.