This application continues to focus on the development and utilizationof immunological methods for monitoring human exposure to environmental carcinogens.
The Specific Aims for the next period are to carry out both aetiologic andmechanistic studies of HCC in Taiwan. Aetiologic studies will continue to focus on three cohorts that have provided subjects for earlier studies by this group on aflatoxin B1 (AFB1) and liver cancer. Three investigations, one simultaneously examining both urine and serum measures of AFB1 exposure, have established the role of this dietary contaminant in HCC in Taiwan. As a next step, this application proposes to investigate the hypothesis that genetic factors influencing metabolism of carcinogens are partly responsible for inter-individual differences in AFB1 adduct levels, by determination of genotype for glutathione S-transferase M1 and T1, and epoxide hydrolase. Since genotyping methods are currently unavailabe to examine the role of polymorphisms in cytochrome P450 3A4 and 1A2, a quantitative immunohistochemical technique for phenotyping will be developed. In addition to HBV and AFB1, cigarette smoking is posited to be a risk factor for HCC in Taiwan. To pursue this possibility, the relationship at the tissue level between smoking and polycyclic aromatic hydrocarbon-and 4-aminobiphenyl-DNA adducts, and oxidative damage (8-hydroxydeoxyguanosine) in liver tissue of cases and controls will be investigated. Since the mechanism responsible for the observed interaction between AFB1 and HBV is unknown, there are plans to assemble a cohort of children and adolescents to test the hypothesis that viral infection influences metabolism of AFB1. Finally, although determination of mechanisms is a major focus, there are also plans to pursue methods for prevention of HCC. Preliminary to an intervention study, current serum levels of several micronutrients in a high risk region will be determined to assess whether subjects living in this area are deficient.
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