AIM: To investigate the association of TNF polymorphisms with chronic atrophic gastritis (CAG) and gastric adenocarcinoma in Chinese Han patients.METHODS: The TNFa-e 5 microsatellites and 3 RFLP sites were typed using PCR technique, followed by high-voltage denaturing PAGE with silver staining and restriction enzyme digestion respectively in specimens from 53 patients with CAG and 56 patients with gastric adenocarcinoma and 164 healthy controls. The PCR products were cloned and sequenced.RESULTS: The frequency of TNF-β Ncol*1/2 genotype was higher in patients with chronic atrophic gastritis than in healthy controls, but no significant difference was observed (60.38% vs 46.34%, P=0.076). The frequency of TNa10 allele was significantly higher in patients with chronic atrophic gastritis than in healthy controls (19.81% vs 11.89%,P=0.04). However, it did not relate to age, gender, atrophic degree or intestinal metaplasia in patients with chronic atrophic gastritis. The frequency of TNF-β Ncol*1/2 and d2/d6 genotypes were significantly higher in patients with gastric adenocarcinoma than in healthy individuals(P＞0.05).However, TNF-β Ncol*1/2 and d2/d6 genotypes did not relate to age, gender, grade of differentiation and clinicopathologic stage in patients with gastric adenocarcinoma. The frequency of TNFa6b5c1 haplotype homozygote was significantly lower in patients with gastric adenocarcinoma than in healthy controls (1.79% vs15.85%, P=0.006).CONCLUSION: TNFa10 allele may be a risk factor for chronic atrophic gastritis. TNF-β Ncol*1/2 and d2/d6 genotypes are associated with the susceptibility to gastric adenocarcinoma,whereas TNFa6b5c1 haplotype homozygote may contribute to the resistance against gastric adenocarcinoma.