Associations of the -238(G/A) and -308(G/A) TNF-α promoter polymorphisms and TNF-α serum levels with the susceptibility to gastric precancerous lesions and gastric cancer related to helicobacter pylori infection in a Moroccan population

Objective: Helicobacter pylori (H. pylori) induces the production of tumor necrosis factor-alpha (TNF-a), which is closely related to a gastric epithelial injury. TNF-a gene polymorphism and TNF-a serum levels are associated with various malignant conditions. Identification of the ideal marker for gastric cancer (GC) is still the leading aim of several trials. Physio-pathological considerations of GC led us to investigate the association of two TNF-a promoter polymorphisms (-308G>A and -238G>A), and TNF-a serum levels with the susceptibility to gastric precancerous (PL) and GC. Methods: Patients suffering from gastric lesions (65 chronic gastritis, 50 PL, 40 GC) related to H. pylori infection , and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNF-a gene promoter sequencing and TNF-a serum levels are measured by ELISA quantitative method. Results: Regarding TNF-a-308 G/A locus, we noticed higher risk for GC (OR=4.3, CI 1.5-11.9, p-value=0.005) and PL (OR=3.4, CI 1.2-9.2, p-value=0.01) for individuals with AA/GA genotypes compared to GG genotype. Concerning TNF-a-238 G/A locus, we noticed higher risk for GC (OR=5.9, CI 1.2-27.5, p-value=0.01) and PL (OR=4.8, CI 1.3-18, p-value=0.01) for individuals with GG genotype compared to AA/GA genotypes. We noticed that TNF-a serum levels have been increased together with gastric lesions severity. Moreover, TNF-a-308 and TNF-a-238 A alleles seemed to, respectively, upregulate and downregulate TNF-a serum levels. Conclusion: The TNF-a -308 A allele has a promotive effect for GC progression, whereas the TNF-a -238 A allele has a protective function against GC progression. High levels of TNF-a seemed to be associated with the aggressiveness of gastric lesions. TNF-a gene polymorphisms and TNF-a serum levels might be helpful to select those patients who are at high risk for GC.