NCI collaborates with the Shanghai Cancer Institute on a large population-based case-control study of biliary tract cancer (over 3,000 subjects) that was designed to investigate the etiology of biliary tract cancer by anatomic subsite (gallbladder, extrahepatic bile duct, and ampulla of Vater). The extensive collection of epidemiologic information and biological samples (serum, DNA, bile, gallstones, urine, and tissue) represents a rich resource on which to test emerging hypotheses in a timely fashion. Fieldwork is complete, and to date, this study has resulted in over thirty publications, yielding many important etiologic leads for gallstones and biliary tract cancer. Gallstones, family history of gallstones, higher parity (for gallbladder cancer), obesity, diabetes, metabolic syndrome, history of chronic liver conditions, history of cholecystitis, and chronic hepatitis B infection were associated with increased risk of biliary tract cancer, while tea drinking and aspirin use were associated with reduced risk.