Abstract CN05-03: Lifestyle, infection, and genetic factors in relation to biliary tract cancer

Biliary tract cancers include tumors of the gallbladder, extrahepatic bile duct, and ampulla of Vater. These cancers are relatively uncommon in most parts of the world, with a reported age-adjusted incidence of less than 10 per 100,000 in most populations. However, South Americans, native Americans, East Europeans, and residents of India experience higher incidence rates. Of the three anatomical subsites, gallbladder cancer is the most common, while cancer of the ampulla of Vater is least common, with rates generally lower than 1.0 per 100,000. Gallbladder cancer is one of the few cancers with female dominance, while extrahepatic bile duct cancer is generally more common in men. Of great interest is the fact that Chile and India have very high rates of gallbladder cancer (>30 per 100,000) but relatively low rates of bile duct and ampulla of Vater cancer. Differences in geographic and gender patterns as well as molecular profiles for these three cancers support the hypothesis that these three anatomic subsites have distinct etiologies. Apart from gallstones, the etiology of biliary tract cancer is unclear, but data from epidemiologic studies suggest that family history of gallstones, higher parity (for gallbladder cancer), obesity, diabetes, metabolic syndrome, history of chronic liver conditions, and history of cholecystitis are associated with increased risk, while tea drinking and aspirin use are associated with reduced risk. It has been reported that chronic hepatitis B infection is associated with a 2-fold risk of extrahepatic bile duct cancer in Shanghai, an endemic area for hepatitis B infection. Similarly, in Chile and India, endemic areas for typhoid fever, it has been suggested that chronic typhoid carriage may increase the risk of gallbladder cancer and help explain partially the unusually high risk of gallbladder cancer in those two countries. To date, most of the epidemiologic findings appear to have a common biological basis, inflammation, which was confirmed by recent genetic data, showing that variants in inflammation-related genes are associated with gallstones and with biliary tract cancer. Genes involved in lipid metabolism, in particular ABCG5 , have also been shown to be associated with a higher risk of gallstones and gallbladder cancer risk. Although having gallstones is the predominant risk factor for gallbladder cancer, additional risk factors (cofactors) must be required for the development of gallbladder cancer, since only 1% of gallstone patients develop gallbladder cancer. Currently, identification of other risk factors is the most critical challenge for biliary tract cancer research. A better understanding of the role of cofactors will help identify a subset of the population with an extremely great need for primary prevention or early detection of biliary tract cancer. Citation Format: Ann W. Hsing. Lifestyle, infection, and genetic factors in relation to biliary tract cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN05-03.