Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer

In Western countries, polymorphism of pro-inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha with susceptibility to peptic ulcer diseases and gastric cancer in Japan. The IL-1 beta-511/-31 and TNF-alpha-308/-857/-863/-1031 genotypes were determined in Helicobacter pylori-positive patients with gastritis only (n = 164), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H. pylori-negative controls (n = 172). Carriage of the alleles TNF-alpha-857 T (odd ratio [OR], 1.826; 95% confidence interval [CI], 1.097-3.039), TNF-alpha-863 A (OR, 1.788; 95% CI, 1.079-2.905) and TNF-alpha-1031 C (OR, 1.912; 95% CI, 1.152-3.171) was associated with increased risk for gastric ulcer development. Carriage of the alleles TNF-alpha-857 T (OR, 1.686; 95% CI, 1.003-2.832), TNF-alpha-863 A (OR, 1.863; 95% CI, 1.118-3.107) and TNF-alpha-1031 C (OR 2.074; 95% CI, 1.244-3.457) was also associated with increased risk of gastric cancer development. There was no relationship between the development of H. pylori-related diseases and polymorphisms of IL-1 beta-511/-31 and TNF-alpha-308. The simultaneous carriage of three different high-producer alleles of TNF-alpha-857/-863/-1031 significantly increased the risk of gastric ulcer (OR, 6.57; 95% CI, 2.34-18.40) and gastric cancer (OR, 5.20; 95% CI, 1.83-14.78). Polymorphisms in TNF-alpha rather than IL-1 beta are associated with increased risk for gastric ulcers and gastric cancer in Japan. The simultaneous carriage of more than one high-producer allele of TNF-alpha further increased the risks for gastric ulcer and cancer.