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Journal of Cancer Prevention

Original Article

J Cancer Prev 2020; 25(3): 164-172

Published online September 30, 2020

© Korean Society of Cancer Prevention

Gallstones, Cholecystectomy and the Risk of Hepatobiliary and Pancreatic Cancer: A Nationwide Population-based Cohort Study in Korea

Dan Huang1,2 , Joonki Lee1,2 , Nan Song3,4 , Sooyoung Cho1 , Sunho Choe1 , Aesun Shin1,3

1Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, 2Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, 3Cancer Research Institute, Seoul National University, Seoul, Korea, 4Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA

Correspondence to :
Aesun Shin, E-mail:,

Received: September 8, 2020; Revised: September 21, 2020; Accepted: September 21, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several epidemiological studies suggest a potential association between gallstones or cholecystectomy and hepatobiliary and pancreatic cancers (HBPCs). The aim of this study was to evaluate the risk of HBPCs in patients with gallstones or patients who underwent cholecystectomy in the Korean population. A retrospective cohort was constructed using the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Gallstones and cholecystectomy were defined by diagnosis and procedure codes and treated as time-varying covariates. Hazard ratios (HRs) in relation to the risk of HBPCs were estimated by Cox proportional hazard models. Among the 704,437 individuals who were included in the final analysis, the gallstone prevalence was 2.4%, and 1.4% of individuals underwent cholecystectomy. Between 2002 and 2015, 487 and 189 individuals developed HBPCs in the gallstone and cholecystectomy groups, respectively. A significant association was observed between gallstones and all HBPCs (HR 2.16; 95% CI 1.92-2.42) and cholecystectomy and all HBPCs (HR 2.03; 95% CI 1.72-2.39). However, when 1-, 3-, and 5-year lag periods were applied, the HBPC and subsites risk approached zero. A significant association was observed between cholecystectomy and intrahepatic bile duct cancer (IBDC) (HR 2.68; 95% CI 1.63-4.40). When 1-, 3- and 5-year lag periods were applied, the IBDC risk after cholecystectomy was 2.86-fold (95% CI 1.68-4.85), 2.92-fold (95% CI 1.51-5.64), and 4.08-fold (95% CI 1.94-8.61) higher, respectively, than that in the comparison group. In conclusion, gallstone diagnosis and cholecystectomy seem to correlate with HBPCs, especially cholecystectomy and IBDC.

Keywords: Gallstones, Cholecystectomy, Liver neoplasms, Biliary tract neoplasms, Pancreatic neoplasms


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