The GST (M, T, P and A) genes polymorphisms in esophageal cancers

Daciana Chirilă, Mihaela Chirilă, Nicolae Turdeanu, Tudor Pop, M Chirilă
enzymes (Jakobsson et al 1999). The mammalian cytosolic GSTs are dimeric, having subunits of 199-244 amino acids in length. Presently there are seven known classes of mam-malian cytosolic GSTs: Alpha, Mu, Pi, Sigma, Theta, Omega, and Zeta (Armstrong 1997; Hayes&McLellan 1999; Board et al 2000). Many other classes of cytosolic GST have been discovered in non-mammalian species (Sheehan et al 2001; Ding et al 2003): Beta, Delta, Epsilon, Lambda, Phi, Tau, "U" class. The GST isoenzymes share
more » ... nzymes share 75%-95% protein sequence identity (Pearson et al 1993) but members of different classes show less than 30% protein sequence identity. The null genotype of the GSTM1 or GSTT1 gene may cause a complete absence of GST enzyme activity, which decreases the ability of detoxify-ing electrophilic compounds, which in turn increases the susceptibility to many malignant tumors (Hayes&Strange 2000; Cheng et al 2012; Deakin et al 1996). Implication of GST polymorphisms in esophageal cancer (EC) GSTP1 Ile105Val was identified as a modest excess risk factor for Barrett esophagus (BE) and esophageal adenocarcinoma in Caucasian males (OR= 1.50, 95% confidence interval [CI] 1.16-1.95; OR (EAC)= 1.20, 95% CI 0.94-1.54) in a 2009 me-ta-analysis of 786 cases with EAC and 509 BE cases from 12 studies (Bull et al 2009). Another 2009 meta-analysis (Zendehdel et al 2009) found that the GSTP1 polymorphism was associated with the risk of es-ophageal squamous cell carcinoma among Caucasians (OR= 1.4; 95% CI 1.0-2.2; p value for heterogeneity test 0.34). Abstract. Glutathione S-transferases (GSTs) are a family of important enzymes which contribute to detoxifications of the cells, protecting the cells against toxic and genotoxic effect of exo-and endogenous substances. The GSTs catalyze the reaction of binding glutathione with a great number of pharmacologically active substances, including those with genotoxic properties. In recent years were much studied the alpha, mu, pi and theta classes of GST. The patients with a null genotype of GSTM1 and GSTT1 genes have a complete absence of the corresponding enzymes activity; in the case of other GSTs enzyme activity may decrease and this may lead to malignant alteration. We were able to observe links between many GST polymorphisms and diverse types of cancers, including digestive cancers. Our objective was to review data concerning the involvement of GST polymorphisms associated with the development of esophageal cancers. Although there have been many conflicting reports regarding this relationship, the current evidence indicates that some GST genotypes are associated with an increase in the risk of esophageal cancers depending on different ethnicities.