Light-to-Moderate Alcohol Consumption Increases the Risk of Biliary Tract Cancer in Prediabetes and Diabetes, but Not in Normoglycemic Status: A Nationwide Cohort Study

To determine whether the dose-response association between alcohol consumption and the risk of biliary tract cancer (BTC), including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), differs according to glycemic status.This nationwide cohort study included 9,520,629 individuals age ≥ 20 years without a history of cancer who underwent national health screening under the Korean National Health Insurance Service in 2009. The participants were followed up until December 2018 for BTC development. Cox proportional hazard regression analysis was performed to estimate risk.During the 78.3 million person-years of follow-up, 21,079 patients were newly diagnosed with BTC. In individuals with prediabetes and diabetes, light-to-moderate alcohol consumption increased the risk of CCA (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.13 to 1.28 and aHR, 1.58; 95% CI, 1.47 to 1.69) and GBC (aHR, 1.18; 95% CI, 1.07 to 1.31 and aHR, 1.45; 95% CI, 1.28 to 1.64). In normoglycemic individuals, light-to-moderate alcohol consumption was not associated with CCA or GBC risk. When heavy alcohol consumption was combined with diabetes, CCA and GBC risk increased synergistically (aHR, 2.04; 95% CI, 1.83 to 2.26; and aHR, 1.65; 95% CI, 1.33 to 2.04, respectively; all P < .001). Prediabetes and heavy alcohol consumption had a synergistic interactive effect on CCA and GBC risks (all P < .001). Comparable results were obtained for intrahepatic and extrahepatic CCA analyses.Even light-to-moderate alcohol consumption was associated with an increased risk of BTC in individuals with prediabetes and diabetes, but not in normoglycemic individuals. Complete avoidance of alcohol consumption may help reduce the risk of BTC in patients with prediabetes and diabetes, suggesting the need for individualized prevention strategies for BTC.