the role of tumor necrosis factor-î±î±| 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)-î±| has a key role in helicobacter pylori -induced gastritis. we analyzed the association between tnf-î± 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-î± at position 308 (g-a transition). h. pylori infection was determined by elisa assay in 100 patients. results the frequencies of tnf-î± 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-î± 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-î± 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.