pylori infection is the initiation of an inflammatory response in which cytokines are the main mediators. Genetic polymorphisms can either accentuate or attenuate the host’s response to inflammation, thus affecting the interaction with environmental factors and H. pylori, the pattern and severity of gastric inflammation and the clinical outcome. Interleukin (IL)-1β is a potent proinflammatory cytokine and is involved in the host’s response to many antigenic challenges. El Omar et al. studied the correlation of these IL-1β genotypes with hypochlorhydria Selleckchem PF-2341066 and gastric atrophy in a Caucasian population of gastric cancer relatives. Genetic polymorphisms in the

IL-1 gene cluster significantly increased the risk of precancerous gastric lesions.27 There is a strong association between genetic polymorphisms

in the IL-1β gene cluster27–30 in tumor necrosis factor-α, IL-1031 and in the IL-8 promoter,32,33 and the risk of gastric cancer. Interestingly a meta-analysis of the role of IL-1β and IL-1 receptor antagonist gene polymorphisms in gastric cancer risk showed an association in Caucasians, but not in Asians.34 Apart from genetic polymorphisms in proinflammatory genes, differences in tumor suppressor genes may be important. RUNX3, a member of the human runt-related transcription factor family, is a possible tumor suppressor gene for gastric cancer.35 RUNX3 expression is ZD1839 solubility dmso frequently suppressed by promoter hypermethylation in gastric cancer cell lines and tissues. A recent study showed that persistent H. pylori infection could induce RUNX3 methylation, with the subsequent loss of RUNX3 expression potentially affecting gastric carcinogenesis.36 Another recent study attempted to identify RUNX3 target genes that promote cell–cell contact. Tumorigenic RUNX3-negative gastric epithelial cells attach weakly to each other, compared with non-tumorigenic, RUNX3-positive cells. It was found that the promoter activity of the gene that encoded the tight junction protein claudin-1 was upregulated via the binding of RUNX3 to the RUNX

consensus sites. The tumorigenicity of gastric epithelial cells from RUNX3-negative mice was significantly reduced by restoration of claudin-1 expression, whereas knockdown of claudin-1 increased the tumorigenicity of human gastric find more cancer cells. It was concluded that the tight junction protein claudin-1 was a direct transcriptional target of RUNX3.37 All these serve to highlight the complex interactions between host and bacterial factors. Environmental factors that have been implicated include salt-preserved food and dietary nitrite, smoking and even metabolic disturbances such as hyperglycemia and hyperlipidemia. In an ecological study, the respective importance of high salt and nitrate intake for gastric cancer mortality was assessed at the population level in 24 countries.38 There was a significant correlation between gastric cancer mortality and sodium as well as nitrate in both men and women.