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

Abstract

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 AFB 1-albumin adducts. Results: There was a dose-response relationship between urinary AFM 1 levels and risk of hepatocellular carcinoma in chronic hepatitis B virus carriers. Comparing the highest with the lowest tertile of urinary AFM 1 levels, the multivariate-adjusted odds ratio (OR) was 6.0 (95% confidence interval (CI) = 1.2–29.0). The hepatocellular carcinoma risk associated with AFB 1 exposure was more striking among the hepatitis B virus carriers with detectable AFB 1-N 7-guanine adducts in urine. Compared with chronic hepatitis B virus carriers who were negative for AFB 1-albumin adducts and urinary AFB 1-N 7-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=1.6–60.9). The proportion of AFB 1 converted to AFM 1 decreased with the progress of liver disease, whereas the formation of AFP 1 increased. The difference in patterns of AFB 1 metabolite formation was an independent risk factor for hepatocellular carcinoma after adjustment for total AFB 1 excretion. There was a synergistic interaction between glutathione S-transferase M1 genotype and AFB 1 exposure in hepatocellular carcinoma risk. Conclusions: AFB 1 intake and expression of enzymes involved in AFB 1 activation/detoxification may play an important role in hepatitis B virus-related hepatocarcinogenesis.