Threshold Dose-Response Association Between Alcohol Consumption and Risk of Young-Onset Pancreatic Cancer: A Nationwide Korean Cohort Study of Young Adults Age 20-39 Years

PURPOSE The incidence of young-onset pancreatic cancer has increased rapidly; however, the dose-response relationship between alcohol consumption and the risk of incident young-onset pancreatic cancer remains unclear. METHODS A nationwide cohort of 6,263,770 individuals age 20 to 39 years who underwent national health screening in Korea between 2009 and 2012 was followed until December 2020. Heavy alcohol consumption was defined as ≥30 g/day for men and ≥16 g/day for women. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs. RESULTS A total of 1,515 cases of young-onset pancreatic cancer were identified. The cumulative incidence was consistently higher among heavy drinkers compared with nondrinkers or light-to-moderate drinkers (log-rank P < .001). Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer (aHR, 1.19 [95% CI, 1.004 to 1.42]), whereas light-to-moderate consumption was not (aHR, 1.04 [95% CI, 0.92 to 1.17]). In addition, alcohol consumption ≥3 times per week was associated with an increased risk (aHR, 1.23 [95% CI, 1.01 to 1.51]). No significant interactions were observed across most subgroups, including age, sex, obesity, smoking status, diabetes, and pancreatitis (all P for interaction > .05), except for physical activity ( P = .011). CONCLUSION Heavy alcohol consumption was significantly associated with an increased risk of young-onset pancreatic cancer in a threshold dose-response manner. These findings suggest that early public health strategies to reduce heavy alcohol consumption among young adults may help mitigate the growing burden of young-onset pancreatic cancer.