Biochemical epidemiology of gallbladder cancer

To evaluate the a priori hypotheses that an increaed level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospital in La Paz, Bolivia, and at one hopital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholethiasis or choledocholithiasis in the abence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well a blood, bile, and gallstone specimens when feasible. Sera were analized for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile pecimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phopholipids; and the glycine and taurine conjugate of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate cotent. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone and 8.2 nmol/L for nonstone controls, P ≤ .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 μmol/mL vs. 33.09 μmol/mL and 154.0 μmol/L, respectively, P ≤ .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the case as well (median 1.70 μmol/mL vs. 4.90 μmol/mL and 16.81 μmol/mL, respectively, P ≤ .02), as was the concentration of bile phopholipids (median 2.97 μmol/mL vs. 6.26 μol/mL and 52.69 μmol/mL, P = .1 and .0004, repectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of non-sulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the diseae process, or may provide useful clues to its pathogenesis.