Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma

Am J Hum Genet. 1996 Jul;59(1):128-34.


This study was carried out to elucidate the effect of glutathione S-transferase (GST) Ml and Tl polymorphisms on the aflatoxin-related hepatocarcinogenesis among chronic carriers of hepatitis B surface antigen (HBsAg). A total of 32 newly diagnosed hepatocellular carcinoma (HCC) cases and 73 age-matched controls selected from a cohort of 4,841 chronic HBsAg carriers who had been followed for 5 years were studied. The level of aflatoxin B1 (AFB1)-albumin adducts in their serum samples collected at the recruitment was examined by competitive enzyme-linked immunosorbance assay, and genotypes of GST M1 and T1 were determined by PCR. There was a dose-response relationship between serum level of AFB1-albumin adducts and risk of HCC. The biological gradients between serum AFB1-albumin adducts level and HCC risk were observed among chronic HBsAg carriers who had null genotypes of GST M1 and/or T1 but not among those who had non-null genotypes. The multivariate-adjusted odds ratios of developing HCC for those who had low and high serum levels of AFB1-albumin adducts compared with those who had a undetectable adduct level as the referent (odds ratio = 1.0) were 4.1 and 12.4, respectively, for HBsAg carriers with null GST M1 genotype (P < .01, on the basis of the significance test for trend); 0.7 and 1.4 for those with non-null GST Ml genotype (P = .98); 1.8 and 10.2 for those with null GST T1 genotype (P < .05); and 1.3 and 0.8 for those with non-null GST T1 genotype (P = .93). The interaction between serum AFB1-albumin adduct level and polymorphisms of GST M1 and T1 was at marginal statistical significance levels (.05 < P < .10).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aflatoxin B1 / blood
  • Aflatoxin B1 / toxicity*
  • Aflatoxins / analysis
  • Aged
  • Albumins / analysis
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / etiology*
  • Carrier State* / enzymology
  • Cohort Studies
  • Genotype
  • Glutathione Transferase / genetics*
  • Hepatitis B / complications*
  • Hepatitis B / enzymology
  • Hepatitis B / genetics*
  • Hepatitis B Surface Antigens / blood
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Risk Factors
  • Taiwan


  • Aflatoxins
  • Albumins
  • Hepatitis B Surface Antigens
  • aflatoxin-albumin adduct
  • Aflatoxin B1
  • Glutathione Transferase