Journal Article

Genetic polymorphisms of glutathione <i>S</i>-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: a nested case–control study in Taiwan

Chien-An Sun, Li-Yu Wang, Chien-Jen Chen, Sheng-Nan Lu, San-Lin You, Lian-Wen Wang, Qiao Wang, Der-Ming Wu and Regina M. Santella

in Carcinogenesis

Volume 22, issue 8, pages 1289-1294
Published in print August 2001 | ISSN: 0143-3334
Published online August 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.8.1289
Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: a nested case–control study in Taiwan

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This study was conducted to investigate the modifying effect of glutathione S-transferase (GST) M1 and T1 polymorphisms on aflatoxin-induced hepatocarcinogenesis among chronic hepatitis B virus surface antigen (HBsAg) carriers. A total of 79 HBsAg-positive cases of hepatocellular carcinoma (HCC) diagnosed between 1991 and 1997 were identified and individually matched to one or two HBsAg-positive controls on age, gender, residence and date of recruitment from the same cancer screening cohort in Taiwan. Blood samples were tested for hepatitis B and C viral markers by enzyme immunoassay and for aflatoxin B1 (AFB1)–albumin adducts by competitive enzyme-linked immunosorbent assay. GSTM1 and GSTT1 genotypes were determined by PCR. There was a statistically significant relationship between detectable levels of AFB1–albumin adducts in serum and risk of HCC among chronic HBsAg carriers, with an adjusted odds ratio (OR) of 2.0 [95% confidence interval (CI) 1.1–3.7]. In addition, the effect of aflatoxin exposure on HCC risk was more pronounced among chronic HBsAg carriers with the GSTT1 null genotype (OR 3.7, 95% CI 1.5–9.3) than those who were non-null (OR 0.9, 95% CI 0.3–2.4). The interaction between serum AFB1–albumin adduct level and GSTT1 genotype was statistically significant (P = 0.03). For GSTM1 the effect of aflatoxin exposure on HCC risk in those with the null genotype was also greater (adjusted OR 2.8, 95% CI 1.0–7.8) than in those with the gene present (adjusted OR 1.8, 95% CI 0.8–4.5), but the difference was not significant (P = 0.91). Notably, when the interaction between aflatoxin exposure and GSTT1 genotype was considered, aflatoxin exposure by itself was not a significant determinant of HCC risk among chronic HBsAg carriers. These results demonstrate the importance of gene–environment interactions in the multifactorial development of HCC.

Keywords: AFB1, aflatoxin B1; AFP, α-fetoprotein; ALT, alanine transaminase; AST, aspartate transaminase; CI, confidence interval; GST, glutathione S-transferase; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HCV, hepatitis C virus; mEH, microsomal epoxide hydrolase; OR, odds ratio.

Journal Article.  5224 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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