Gallstones and the Risk of Gallbladder Cancer Mortality: A Cohort Study.

OBJECTIVES: Despite epidemiologic data, definitive evidence for the role of gallstones as a cause for gallbladder cancer is lacking. The goal of this study was to evaluate the association between gallstones, determined by ultrasound, and the risk of gallbladder cancer mortality in a large study of Korean men and women. In addition, the association between gallstones and cholecystectomy, and risk of hepatobiliary cancer mortality was investigated.

METHODS: A cohort study was performed for 396,720 South Korean men and women who underwent a health checkup from 2002 to 2012. Hazard ratios for mortality outcomes were estimated using Cox-proportional hazards regression analysis. Vital status and cause of death assignment were based on linkage to the National Death Index of death certificate records.

RESULTS: From a total of 2,158,906.2 person-years of follow-up (median follow-up of 5.4 years), we identified 224 deaths from hepatobiliary cancer, comprising 174 cases of liver/intrahepatic bile ducts cancer, 20 cases of gallbladder cancer, and 30 cases of biliary tract cancer. Gallstones were significantly associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic biliary cancer, and gallbladder cancer mortality. The multivariable-adjusted hazard ratios (95% confidence intervals) for hepatobiliary cancer, liver/intrahepatic biliary cancer, and gallbladder cancer mortality comparing subjects having gallstones with those without gallstone disease were 2.74 (1.83-4.10), 2.34 (1.45-3.77), and 7.35 (2.60-20.8), respectively. Cholecystectomy was not significantly associated with hepatobiliary cancer mortality.

CONCLUSIONS: In this large cohort study, gallstones were associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic cancer, and gallbladder cancer mortality independent of potential confounders. Future studies with longer follow-up periods that include data on incident cancer cases should provide a more comprehensive view of the role of gallstones in cancer development.