The TNF-A–857*T polymorphism is associated with gastric adenocarcinoma risk in a Costa Rican population

Abstract

Background: Costa Rica is ranked as one of the countries with highest incidence of gastric cancer worldwide. Previous studies in Costa Rican populations have revealed associations between gastric cancer risk and several cytokine polymorphisms that seem to play a role in the regulation of the expression of these proteins. In this study, we assessed associations of the polymorphisms IL-6-174 G/C, IFNGR1-56 C/T, IL-8-251 T/A and TNF-A (-857 C/T, -308 A/G) with gastric pathologies in a high-risk population of Latin America. Methods: DNA samples of 47 patients with gastric adenocarcinoma, 53 with chronic gastritis, 56 with duodenal ulcer and 94 healthy controls, were genotyped for the five mentioned SNPs. All participants were ≥50-years-old. Genotyping was performed by PCR-RFLP and 5’-nuclease PCR assay. H. pylori infection, CagA status, pepsinogen (PG) I and II blood levels were determined by ELISA. Logistic regression analysis was used to determine possible associations of the polymorphisms with cancer, gastritis and duodenal ulcer, and linear regression analysis to determine associations with blood PG levels. Results: A total of 86.6% of the population was positive for H. pylori; of them, 51.6% was CagA+. Patients with the TNF-A857*T allele had an increased risk for gastritis (OR: 3.67, p = 0.015) and gastric adenocarcinoma (OR:6.15, p = 0.001). Associations between other polymorphisms and gastric diseases, or PG levels, were not found. Conclusions: Our results indicate that the TNF-A-857*T SNP is among the risk factors associated with the risk of gastric cancer in Costa Rica