The Link Between Specific Haplotype of Tumor Necrosis Factor Alpha and Interleukin-۱β Polymorphisms in Promoter Region with Helicobacter Pylori Infection and Gastric Carcinogenesis

Background and Aim : The infection with Helicobacter pylori (H. pylori) and cytokine-mediated inflammatory responses plays significant roles in the pathogenesis of gastric cancer (GC). To determine a link between the risks of GC and genetic polymorphisms in tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-۱β, this study was performed.Methods : The polymorphisms of IL۱B and TNFA genes were analyzed by PCR-RFLP in ۲۹۰ patients who underwent endoscopy. H. pylori infection was affirmed by rapid urease test, histological analysis, and gastric biopsy PCR. The quantitative real-time PCR was performed to determine the relative mRNA expression levels. Results : There were no significant differences in allele frequencies and genotype for all explored polymorphisms between chronic gastritis, GC and healthy individuals. Interleukin ۱β mRNA was down-regulated in both the gastritis group (Relative Quantification (RQ)=۰.۴۴۷) and the GC group (RQ=۰.۱۵۱). In contrast, the expression of TNF-α were increased in the GC group (RQ=۲.۸۱۷) in relation to the gastritis group, which was down-regulated (RQ=۰.۸۶۱). Conclusion : The studied single-nucleotide polymorphisms are not risk factors for development of chronic gastritis and GC. However, the H. pylori infection causes a huge increase in the expression of TNF-α in GC patients.

کلیدواژه ها:

gastric cancer ، cytokines ، chronic gastritis ، gene polymorphisms ، Helicobacter pylori