Risk factors of biliary tract cancer in a large-scale population-based cohort study in Japan (JPHC study); with special focus on cholelithiasis, body mass index, and their effect modification

Objectives We examined the association of potential risk factors with the incidence of biliary tract cancer in a large-scale population-based cohort study. Particular focus was placed on a history of cholelithiasis, body mass index (BMI), and their effect modification, and whether risk differs by cancer subsite, namely by gallbladder cancer and extrahepatic bile duct cancer. Design We investigated 101,868 middle-aged and older Japanese subjects (48,681 men and 53,187 women) during 1,200,386 person-years of follow-up. Results A total of 235 cases of biliary tract cancer (93 gallbladder cancer and 142 extrahepatic bile duct cancer) were newly diagnosed. Cholelithiasis was associated with an increased risk of biliary tract cancer [HR, 2.53; 95% CI, 1.56-4.12]. This association was similarly observed for both gallbladder [HR, 3.01; 95% CI, 1.56-6.19] and extrahepatic bile duct cancer [HR, 2.12; 95% CI, 1.08-4.18]. Body mass index was associated with an increased risk of extrahepatic bile duct cancer (P for trend = 0.03) and this effect was not modified by a history of cholelithiasis. Conclusions Cholelithiasis was confirmed to be associated with the risk of biliary tract cancer, both gallbladder and extrahepatic bile duct cancer. Obesity may increase the risk of extrahepatic bile duct cancer only, independent of cholelithiasis.