Abstract
BACKGROUND: We investigated the relationship between intakes of red, white, and processed meats with liver cancer-including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, gallbladder cancer, and other biliary tract cancers. METHODS: The analytic cohort consisted of 480 347 US adults in the prospective National Institutes of Health-AARP Diet and Health Study who were cancer-free at baseline at ages 50-71 years. With a median follow-up of 19.68 years, we identified 1150 participants with incident liver cancer (219 intrahepatic cholangiocarcinomas and 931 hepatocellular carcinomas), 231 with incident gallbladder cancer, and 472 with other incident biliary tract cancers (272 extrahepatic cholangiocarcinomas). At baseline, a self-administered food frequency questionnaire assessed usual dietary intake. We used multivariable Cox proportional hazards models to estimate the associations of meat type with hepatobiliary cancers. We used substitution models with the "leave-one-out" approach as our primary analysis and addition models as a supplemental analysis. RESULTS: Replacing red meat with white meat was inversely associated with liver cancer (hazard ratio [HR]50 g/1000 kcal = 0.62, 95% CI = 0.51 to 0.77), hepatocellular carcinoma (HR50 g/1000 kcal = 0.63, 95% CI = 0.50 to 0.80), and intrahepatic cholangiocarcinoma (HR50 g/1000 kcal = 0.56, 95% CI = 0.35 to 0.90). Because of the symmetry of substitution models, replacing white meat with red meat yielded hazard ratios equal to the reciprocal of these values, indicating increased risk for the same cancer sites. No associations were observed for meat intake and gallbladder or other biliary tract cancers. CONCLUSIONS: Our study indicates replacing intake of red meat with white meat could lower risk of liver cancer by nearly 40%, whereas replacing white meat with red meat could increase the risk by more than 60%.