Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan.
OBJECTIVE
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 = 1.6-60.9). 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.
Yu
M W
MW
School of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
Lien
J P
JP
Chiu
Y H
YH
Santella
R M
RM
Liaw
Y F
YF
Chen
C J
CJ
D000328:Adult; D000348:Aflatoxins / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D002353:Carrier State; D002908:Chronic Disease; D018736:DNA Adducts / Q000096:biosynthesis*; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D000348:Aflatoxins; D018736:DNA Adducts