title: Gallstones and the Risk of Gallbladder Cancer Mortality: A Cohort Study.
abstract: OBJECTIVE
  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.
authors: Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.
authors: Seungho
authors: S
authors: Ryu
authors: Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.
authors: Yoosoo
authors: Y
authors: Chang
authors: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Kyung Eun
authors: KE
authors: Yun
authors: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Hyun-Suk
authors: HS
authors: Jung
authors: Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Jun Ho
authors: JH
authors: Shin
authors: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Hocheol
authors: H
authors: Shin
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000401:mortality; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D002277:Carcinoma / Q000401:mortality*; D018281:Cholangiocarcinoma / Q000401:mortality; D002763:Cholecystectomy; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000401:mortality*; D042882:Gallstones / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies