The Interaction between<i> GSTT1</i>,<i> GSTM1</i>, and<i> GSTP1</i> Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk

Abstract

The study investigated the possible influence of <i>GSTM1</i>, <i>GSTT1</i>, and <i>GSTP1</i> gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with <i>H. pylori</i> infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (<i>p</i> = 0.01) as well as in premalignant lesions (<i>p</i> = 0.01). The <i>GSTM1</i> null genotype increased the risk for mucosal defects in <i>H. pylori</i>-negative patients (OR = 2.27, 95% CI: 1.20-4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19-3.83). The <i>GSTT1</i> deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72-4.74). The combined <i>GSTT1T1</i> and <i>GSTM1</i> null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00-2.97). The wild-type <i>GSTP1</i> Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37-0.98). In conclusion, the <i>GSTM1</i> and <i>GSTT1</i> null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by <i>H. pylori</i>, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.