Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan

Background/Aims: Aflatoxins (AFs) are established hepatic carcinogens in several animal species. This study was performed to establish whether aflatoxin exposure may affect the risk of developing hepatocellular carcinoma in chronic hepatitis B virus carriers. Methods: Urinary AF metabolites were measured for 43 HCC cases and 86 matched controls nested in a cohort of 7342 men in Taiwan. Thirty hepatocellular carcinoma cases and 63 controls were also tested for AFB₁-albumin adducts. Results: There was a dose-response relationship between urinary AFM₁ levels and risk of hepatocellular carcinoma in chronic hepatitis B virus carriers. Comparing the highest with the lowest tertile of urinary AFM₁ levels, the multivariate-adjusted odds ratio (OR) was 6.0 (95% confidence interval (CI)=1.2-29.0). The hepatocellular carcinoma risk associated with AFB₁ exposure was more striking among the hepatitis B virus carriers with detectable AFB₁-N⁷- guanine adducts in urine. Compared with chronic hepatitis B virus carriers who were negative for AFB₁-albumin adducts and urinary AFB₁-N⁷-guanine, no elevated risk was observed for those who were positive for either marker. But an extremely high risk of hepatocellular carcinoma among those having both markers was found (OR=10.0, 95% CI=1.6-0.9). The proportion of AFB₁ converted to AFM₁ decreased with the progress of liver disease, whereas the formation of AFP₁ increased. The difference in patterns of AFB₁ metabolite formation was an independent risk factor for hepatocellular carcinoma after adjustment for total AFB₁ excretion. There was a synergistic interaction between glutathione S-transferase M1 genotype and AFB₁ exposure in hepatocellular carcinoma risk. Conclusions: AFB₁ intake and expression of enzymes involved in AFB₁ activation/detoxification may play an important role in hepatitis B virus-related hepatocarcinogenesis.