title: Glutathione-S-transferase and microsomal epoxide hydrolase polymorphism and viral-related hepatocellular carcinoma risk in India.
abstract: Hepatocellular carcinoma (HCC) is the fourth most common cancer worldwide, the main etiological factors being chronic infections with hepatitis B and C viruses. Genetic polymorphic forms of glutathione-S-transferase (GST) and microsomal epoxide hydrolase (mEPHX) have been associated with risk for various malignancies. The present study was undertaken to evaluate the association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population. Three groups of subjects were considered, control (n = 169), chronic viral hepatitis (n = 174), and HCC (n = 63). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for this polymorphic study. Genotype distributions between categories were compared using the chi2 test; odds ratios (ORs) and 95% confidence interval were calculated to express the relative risk. GSTT1 null genotype was associated with 2.23-fold (p < 0.05) increased risk for HCC development as compared to the control group. However, GSTM1 null genotype was found to have a protective effect when hepatitis patients were considered. In case of mEPHX, R139R imposed a risk factor for HCC with both control (OR = 1.81) and chronic hepatitis-infected (OR = 2.06) subjects. Combination of heterozygous mutant genotypes at mEPHX exons 3 and 4 revealed a twofold risk (nonsignificant) for HCC. Further, combination of GSTM1 and T1 genotypes with either of exon 3 or 4 polymorphism of mEPHX displayed synergistic associations (risk or protective) for HCC development. GST and mEPHX variants share a positive association with viral-related HCC risk in Indian population, although a larger sample size is still required to confirm the results.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Kiran
authors.forename: Yogesh Kumar
authors.initials: YK
authors.lastname: Chawla
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics / Q000821:virology; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics; D006801:Humans; D007194:India; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D055815:Young Adult
chemical_list: D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1