Integrating Biomarkers into Translational Research on Diet and Cancer

Here, we elucidate dietary factors that contribute to or protect against liver and prostate cancer, and their relationship with underlying pathophysiologic mechanisms. Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. Phytanic acid, one of AMACR’s primary substrates, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. The first study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate. Our data could not unify the hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat. The focus of the second part is vitamin A, iron, and the joint relationship of vitamin A and iron in patients at high risk for liver cancer. HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC). Increased oxidative stress is regarded as a major mechanism of HCV-related liver disease progression. Deficiencies in retinoid and carotenoid antioxidants and increased iron may represent a major modifiable risk factor for HCC progression. We observed that a decrease in serum retinol, β-carotene, and RBP4 is associated with early stage HCV infection. Retinoid and carotenoid levels decline as disease progresses, and our data suggest that this decline occurs early in the disease process, even before fibrosis is apparent. Measures of oxidative stress are associated with fibrosis stage and concurrent antioxidant depletion. Vitamin A loss is accompanied by stellate cell activation in hepatic tissue. We observed an increase in serum iron biomarkers in CLD patients compared to controls. Serum retinoids were inversely associated with serum iron biomarkers. However, there was little evidence of a joint effect between iron and retinoids in early CLD.