Glutathione S-transferases pi 1, alpha 1 and M3 genetic polymorphisms and the risk of hepatocellular carcinoma in humans.

Introduction: Glutathione S-transferases pi1, alpha1 and micro3 are members of an enzymatic superfamily involved in the conjugation and detoxification of carcinogens. Polymorphisms affecting the genes encoding these enzymes may modify their ability to neutralize carcinogens. Our aim was to investigate whether these polymorphisms affect the risk of developing hepatocellular carcinoma in humans.

Methods: A total of 184 white Spanish patients diagnosed with hepatocellular carcinoma and 248 healthy control subjects from the same ethnic origin were included. GSTA1*B promoter allele, GSTM3*B 3-bp-deleted allele and GSTP1 Ile105Val SNP were identified.

Results: No differences were found between the distribution of the studied polymorphisms, or in the allele frequencies for variant alleles in patients and controls: 0.411 and 0.371 for GSTA1, 0.116 and 0.131 for GSTM3, and 0.285 and 0.309 for GSTP1, respectively. Among patients the GSTP1 mutated allele was more frequent in those drinking more than 50 g ethanol/day (odds ratio: 2.00; 95% confidence intervals: 1.06-3.78). Age at diagnosis, gender, tobacco use and hepatitis B and C viral status did not influence these results.

Conclusion: We conclude that the studied polymorphisms affecting GSTP1, GSTA1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.