The Role of Tumor Necrosis Factor-α| Promoter Polymorphisms in Gastric Carcinoma in Iranians: A Case-Control Study in the North-East of Iran

Background Host genetic and environmental factors are involved in development of gastric cancer. Tumor necrosis factor (TNF)-α| has a key role in Helicobacter pylori-induced gastritis. We analyzed the association between TNF-α polymorphism and the risk of gastric cancer in an Iranian population residing in northeastern Iran. Materials and Methods In a case-control study, the genotyping was carried out by PCR-RFLP in 108 patients with gastric cancer and 100 randomly-selected healthy individuals. The polymorphic sites studied include promoter region of TNF-α at position 308 (G-A transition). H. pylori infection was determined by ELISA assay in 100 patients. Results The frequencies of TNF-α 308 GG, AG and AA genotypes were 67%, 29% and 4% for controls and 75.9%, 13.2% and 10.2% for patients. AG genotype significantly reduced the risk of gastric carcinoma (p=0.008). There was no association between TNF-α 308 polymorphisms and the risk of diffuse type gastric carcinoma. Carriers of AG genotype were associated with a decreased risk of intestinal type gastric carcinoma (OR=0.25, 95% CI: 0.08-0.7). With stratification of patients according to H. pylori infection status, there were no significant differences in the frequencies of genotypes between those with H. pylori-negative gastric carcinoma and controls. However, the frequency of AG genotype was significantly higher among controls than H. pylori-positive cases (OR=0.230, 95% CI: 0.06-0.8). In contrast, AA genotype was significantly more frequent among H. pylori-positive cases compared to the controls (OR=4.1, CI: 1.04-16.4). Conclusions Our results suggest an association between TNF-α 308 polymorphism and the risk of gastric cancer in Iranians. The effect is prominent among H. pylori-infected patients and intestinal type of gastric carcinoma.