Gallbladder cancer (GBC) is a relatively uncommon neoplasm, however its prognosis is poor with less than a 5% 5-year survival rate. There are considerable geographic differences in its incidence and etiology. Two main pathways of GBC pathogenesis have been identified. The most common is associated with gallstones and chronic inflammation of the gallbladder, whereas a second, less frequent pathway is associated with a congenital abnormality of the pancreatic bile-duct junction, which is particularly common in Japan. TP53 inactivation has an important and early role in GBC associated with gallstones and chronic inflammation. Although KRAS mutations are rarely detected in GBC associated with gallstones, they are frequent and early events in tumors associated with congenital abnormality of the pancreatic bile-duct junction.
