Promoter polymorphisms of tumor necrosis factor-alpha are associated with risk of gastric mucosa-associated lymphoid tissue lymphoma.

Genes involved in regulating antimicrobial immunity and inflammation may modulate the risk of Helicobacter pylori-associated diseases. IL-1 and TNF-alpha are major cytokines detected in H. pylori-infected tissues. We aimed to determine the role of gene polymorphisms for these cytokines and their receptors in 2 distinct H. pylori-related gastric malignancies, adenocarcinoma (GAC) and maltoma. Genotyping for IL-1beta (-31 C/T, -511 C/T), TNF-alpha (-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C), TNFR1 (-383 A/C) and TNFR2 (196 G/T) was undertaken for 70 patients with maltoma and 204 patients with noncardia GAC and compared to 210 unrelated healthy controls. Genotype frequencies showed no differences among patients with GAC or maltoma and controls for IL-1beta, TNFR1 or TNFR2. The TNF-alpha -857 T variant was significantly underrepresented in maltoma compared to controls (6.4% vs. 14.3%, p = 0.018), conferring a 3-fold decrease in risk (OR = 0.33, 95% CI 0.15-0.75). Comparison of allele frequencies between GAC and controls failed to show any statistical significance for TNF-alpha polymorphisms. We concluded that TNF-alpha -857 T itself or a neighboring gene may modify the risk of maltoma. The differences in genetic background as well as divergent clinicopathologic features between GAC and maltoma support the notion that fundamental mechanistic differences exist in these 2 well-defined H. pylori-related malignancies.