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 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.