Tumor Necrosis Factor-alpha-308G/A Promoter Polymorphism is Associated with the Severity of Gastric Carcinomas

ABSTRACT

PURPOSE: The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), is a central mediator of the immune response involved in a wide range of immuno-inflammatory and infectious diseases. There is increasing evidence that TNF-alpha may promote the development and spread of the cancer. Polymorphisms in the TNF-alpha promoter have been related to TNF-alpha production. Therefore, we investigated the potential association of TNF-alpha genotypes with gastric cancer in the Korean population. METHODS: The study included 66 patients with gastric adenoma, 75 patients with gastric carcinoma, and 551 healthy controls. The -308 and -238 polymorphisms in the TNF-alpha promoter were analyzed by PCR- restriction fragment length polymorphism (RFLP). Distributions of TNF-alpha promoter polymorphisms were compared between groups by chi2 test. P values smaller than 0.05 were considered to be significant. RESULTS: The proportion of individuals carrying the TNF-alpha -308A allele was higher in the carcinoma group compared to controls and adenomas, but the differences were not significant (P=0.124). However, the TNF-alpha -308A allele was significantly associated with advanced gastric carcinoma (P=0.026), serosa invasion (P=0.004), neural invasion (P= 0.021), and lymph node metastasis (P=0.005). On the other hand, the TNF-alpha -238G/A polymorphism was not associated with the development of gastric adenoma and carcinoma and the severity of gastric carcinoma. CONCLUSION: These results suggest that the TNF-alpha -308A allele is associated with the severity of gastric carcinoma in terms of invasion and metastasis in the Korean population. Therefore, TNF-alpha promoter polymorphism could be used as a predictive marker of the severity of gastric carcinoma.