Association of specific haplotype of tumor necrosis factor-alpha and interleukin-1 beta polymorphisms with Helicobacter pylori infection and gastric carcinogenesis

Introduction: The Helicobacter pylori infection and cytokine-mediated inflammatory responses play significant roles in the pathogenesis of gastric cancer (GC). This study was performed to determine the association between the risk of GC and genetic polymorphisms in interleukin (IL)-1 beta and tumor necrosis factor-alpha (TNF-alpha). Methods The polymorphisms of IL-1 beta and TNF-alpha genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 290 patients who underwent endoscopy. Infection with H. pylori was diagnosed by histological analysis, rapid urease test, and PCR of gastric biopsy samples. Quantitative real-time PCR was performed to determine the relative mRNA expression levels. Results No significant difference was detected in allele frequency and genotype of all studied polymorphisms between chronic gastritis (CG), GC and healthy individuals. IL-1 beta mRNA was down-regulated in both gastritis (relative quantification (RQ)=0.447) and the GC groups (RQ=0.151). In contrast, the expression of TNF-alpha was up-regulated in the GC group (RQ=2.817) compared to the gastritis group (RQ=0.861). Conclusions The studied single-nucleotide polymorphisms are not risk factors for development of CG and GC. However, H. pylori infection causes a huge increase in the TNF-alpha expression in GC patients.