Gastric cancer and H. pylori-host factors

Abstract

Helicobacter pylori (H. pylori) is an important causal factors of non-cardia gastric cancer. However, gastric cancer developed in only about 1% of H. pylori infected persons. This indicates that the interactions of host genetic factors, bacterial virulence factors, and environmental factors might contribute to the different outcomes after H. pylori infection. Genetic polymorphisms of proinflammatory cytokine genes (eg. IL-1, TNF-A, and IL-10), E-cadherin genes (CDH1), tumor suppressor genes (eg. p53), and genes involved in the metabolization (eg. MTHFR, GSTT1) have been reported to be associated with susceptibility of sporadic noncardia gastric cancer in several candidate gene approach studies. However, ethnic differences on these issues have been observed in these metaanalyses. IL-1B-511C/T polymorphisms have been shown to be associated with increased risk of gastric cancer in Caucasians, but not in Asians. In contrast, IL-10-1082 A/G polymorphisms have been shown to be associated with increased risk of gastric cancer in Asians, but not in Caucasians. Ethnic differences of genetic polymorphisms at TNF-A, CDH1, TP53, and GSTT1 genes on gastric cancer risk have also been reported. More recently, genome wide association studies showed that genetic polymorphisms in prostate stem cell antigen (PSCA, rs2294008) and mucin 1 (MUC1, rs4072037) genes were associated with risk of diffuse type and intestinal type gastric cancer. The association had been validated in several other populations, including Asians and Caucasians. In conclusion, ethnic differences of genetic polymorphisms at IL-1B, IL-10, TNF-A, CDH1, TP53, and GSTT1 genes on gastric cancer risk have been reported. Genetic polymorphisms at PSCA and MUC1 were associated with gastric cancer risk in both Caucasians and Asians. Further large genetic association studies using the same study design and methods in different ethnic populations are warranted on this issue.