Gallbladder Cancer Risk Factors
The two most common malignancies of the biliary tree are adenocarcinoma of the gallbladder problems and of the bile duct. Although there is some overlap in the diagnosis and treatment of these two cancers, they are distinct enough to require separate discussions. Carcinoma of the gallbladder, which we consider first, is a rare form of cancer and as such has a distinct etiology, pathophsiology, clinical presentation, and treatment. In most patients, the disease is not suspected clinically and is found at an advanced stage, often during gallbaldder surgery for cholelithiasis.
Although gallbladder cancer is a rare form of cancer, it is most common malignancy of the biliary tract and the fifth most common cancer of the gastrointestinal tract. Women develop gallbladder cancer five times more often than men, similar to the incidence of gallstones. Studies have also shown that female sex, age, postmenopausal status and cigarette smoking are risk factors. Other studies have identified overweight and obesity as significant risk factors. Gallbladder cancer is rare in individuals under age 50, with most cases occurring among those in their late 60s and early 70s.
Several factors are associated with an increased risk for gallbladder cancer. Gallstones are the most common etiologic factor, probably due to their high prevalence in the general population. More than 90 percent of individuals with gallbladder cancer have coexistent chorionic cholecystitis and cholelithiasis. Gallbladder cancer is more likely to occur in individuals with a single large gallstone than in those with multiple smaller stones. Patients having gallstones greater than 3 cm have ten times greater risk of developing gallbladder cancer. It is presumed that the large gallstones have been present for a long period of time, causing chronic irritation of the gallbladder wall and thus predisposing it to the development of carcinoma.
Individuals with a choledochal cyst may develop carcinoma throughout the biliary tree, but most tumors arise in the gallbladder. The chance of developing an associated gallbladder or bile duct cancer increases for women beginning at age 40. in their 70s and 80s the ratio of incidence for men to women is about one to three. Recent studies have suggested that an anomalous pancreatobiliary duct junction is associated with an increased incidence of gallbladder cancer in individuals with a choledochal cyst, a congenital cystic dilation of the biliary tree. This common channel abnormality between the common bile duct and pancreatic duct allows reflux of pancreatic juice into the biliary tree. The question still remains whether it is the regurgitation of pancreatic juice or the relation ship of the abnormal junction to bile stasis and the subsequent retention of carcinogens within the biliary tree that causes gallbladder cancer. Further , animal studies have suggested that azotoluence and nitrosamines can cause gallbladder cancer, and an association between gallbladder cancer and obesity and estrogens has been suggested in epidemiological studies. Recent studies, however, have failed to validate the previously held concept that certain industrial carcinogens are linked to gallbladder cancer problems.
Typhoid carries have an increased risk of gallbladder and bile duct cancer. The higher incidence of gallbladder cancer in chronic typhoid carriers is also thought to result from chronic irritation and degradation of bile acids.
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