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.
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).
Chen
C J
CJ
Institute of Epidemiology, College of Public Health, National Taiwan University, Taiwan.
Yu
M W
MW
Liaw
Y F
YF
Wang
L W
LW
Chiamprasert
S
S
Matin
F
F
Hirvonen
A
A
Bell
D A
DA
Santella
R M
RM
D000328:Adult; D016604:Aflatoxin B1 / Q000097:blood / Q000633:toxicity*; D000348:Aflatoxins / Q000032:analysis; D000368:Aged; D000418:Albumins / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000209:etiology*; D002353:Carrier State / Q000201:enzymology; D015331:Cohort Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006509:Hepatitis B / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013624:Taiwan
D000348:Aflatoxins; D000418:Albumins; D006514:Hepatitis B Surface Antigens; C098408:aflatoxin-albumin adduct; D016604:Aflatoxin B1; D005982:Glutathione Transferase