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

Abstract

The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori 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 (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-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 GSTT1 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 GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00–2.97). The wild-type GSTP1 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 GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

Do we really need genetic tests in current clinical practice?

“…MDR1 (or ABCB1) gene polymorphisms C1236T, G2677T, and C3435T were genotyped by PCR-RFLP techniques to investigate the association between the mentioned SNPs and antiepileptic drug concentrations and treatment response (7), clinical course of pediatric pulmonary arterial hypertension (8), and gastric lesions (9). Furthermore, the PCR-RFLP method was applied for analyzing the interleukin-6 SNPs and their correlations with patients' sepsis risk and severity in adult patients (10) for glutathione S-transferase (GST) SNPs in premalignant gastric lesions risk (11) and for investigation of the impact of CYP2C19 polymorphisms in platelet response to clopidogrel (12) and on severity of gastric lesions (9). Nested PCR technique is a variant of PCR that increases the specificity and efficiency of the desired amplicons by using two pairs of PCR primers (outer primers and nested primers).…”

Congestive Heart Failure and Upper Digestive Endoscopic Lesions

“…Many patients with CHF use antithrombotic treatments, antiplatelet and/or anticoagulants. These drugs promote the blood loss by the entire GIT from various mucosal lesions [17,18,19,20]. Furthermore, gastrointestinal conditions that do not usually induce bleeding, frequently associate iron deficiency anemia due to impairment of iron metabolism [21].…”

Chronic Statin Therapy and Histologic Gastric Changes

“…2,12,13 Case-control or observational studies evaluating the interaction between gastric cancer and statin therapy showed a neutral effect, 14,15 while others have noticed a reduced rate of gastric cancer, [16][17][18] , or even an inverse effect.3 The present research identified a statistically significant protective role of statins (p = 0.006) against premalignant lesions in the studied population, while age over 50 years and smoking remain the most important risk factors for premalignant gastric lesions. Statin therapy might have a certain protective effect, but other factors related to the host's genetic susceptibility 19 and the complex interaction with environmental risk factors should be considered in further large models.…”