Updated 20 January 2006

Gallbladder cancer is a rare (<0.5% of all cancers) but aggressive malignancy. It is the fifth most common gastrointestinal malignancy in the United States. Incidence does vary with geographic area. It is particularly high in regions such as South America. In addition, rates of gallbladder cancer are higher in the southwestern Native Americans and Mexican Americans. Incidence of gallbladder cancer increases with age. Women are affected two to six times more often than men. Caucasians are affected more often than those of African descent.

In 75% of cases, gallbladder cancer is seen in association with cholelithiasis. The actual incidence of gallbladder cancer, however, in patients with cholelithiasis remains low at <0.2%. Cholesterol stones are most highly linked, and larger stones may have a higher risk. The risk is also increased with the duration of cholelithiasis, particularly over 40 years. Individuals with symptomatic gallbladder disease were 4.4 fold more likely to develop gallbladder cancer.

Patients with extensive calcification of the gallbladder wall (porcelain gallbladder) should undergo cholecystectomy because this condition is associated with a high incidence of gallbladder cancer (10-25% develop gallbladder cancer with time).

Persisting gallbladder polyps of 0.5 cm or more in diameter should be considered for treatment by cholecystectomy because of the potential for malignancy. There is no means of determining the presence or absence of dysplasia or malignancy other than by cholecystectomy.

Other risk factors for gallbladder cancer include anomalous pancreatic duct drainage, congenital biliary cysts, and chronic Salmonella typhi carriage.

Medications associated with an increase in gallbladder cancer include methyldopa, oral contraceptives and isoniazid.

It is hypothesized that chronic irritation of gallbladder mucosa over a period of years may predispose to malignant transformation. In addition, it appears that bile samples from patients in endemic areas are more mutagenic than from patients in low incidence areas, however, this data is still inconclusive.