Family history of gallstones and the risk of biliary tract cancer and gallstones: A population-based study in Shanghai, China

Biliary tract cancers, encompassing tumors of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are relatively uncommon malignancies in most parts of the world (1). The highest incidence rates have been observed among Native Americans and Hispanics living in the Southwestern United States and among some populations in Central and South America, Eastern Europe, and certain parts of Asia (1,2). Between 1972 to 1994, the incidence rates for biliary tract cancer rose more rapidly than those for any other malignancy in Shanghai, China, with increases of 119% among men and 124% among women (3). The increases in incidence were seen for all three biliary tract subsites in all age groups. Gallstones are the most important risk factor for biliary tract cancers (1,4), especially for gallbladder cancer patients in whom 60-80% have a history of gallstones (1,5,6). Both gallstones and gallbladder cancer occur more frequently among women and older persons. Ethnic and familial predisposition suggests the role of genetic predisposition or shared lifestyle and metabolic factors, including obesity, insulin resistance, or high-fat, high-caloric diet (1,7-9). Familial aggregation of gallstones has been reported in several studies (10-12), but only one assessed the role of family history of gallstones in biliary tract cancer etiology. A case-control study of gallbladder cancer in Bolivia and Mexico reported that family history of gallstones was associated with a 3.6-fold risk of gallbladder cancer (13). The mechanisms are unclear, but it is possible that some yet unidentified susceptibility mechanism may further elevate the risk of biliary tract cancer associated with stones. To investigate the rapid rise in incidence rates of biliary tract cancers in Shanghai, we conducted a large population-based study in Shanghai between 1997 and 2001. In this report, we examined whether a family history of gallstones is an independent risk factor for biliary tract cancer and whether it augments the risk associated with the presence of gallstones.