Molecular epidemiology of gastric cancer: current status and future prospects

Gene-environment interaction appears to contribute to the etiology of gastric cancer, as suggested by the varying geographic patterns of gastric cancer incidence. Even in areas with a high rate Helicobacter pylori (H. pylori) infection, only a small proportion of infected individuals develop gastric cancer. It is likely that genetic factors, particularly relatively common genetic variants, such as single nucleotide polymorphisms (SNPs), may modulate the effects of environmental risk factors by regulating multiple biologic pathways involved in gastric carcinogenesis. Thus, common genetic variants can pose a substantial influence on the population attributable risk, even though the absolute risk associated with each of these variants may be low. Remarkable progress has been made in the field of molecular epidemiology, but it appears that an initial view on the magnitude of the effects of inherited variants was overestimated. Nevertheless, evidence suggests that genetic variants may contribute to the etiology of gastric cancer, particularly those SNPs in genes that are involved in inflammatory response, metabolism of chemical carcinogens, DNA repair, and tumor suppression. Although previous molecular epidemiologic studies of potentially functional polymorphisms in candidate genes and gastric cancer susceptibility lack consistency, they have advanced our knowledge of the role of genetic susceptibility in the etiology of gastric cancer. Future, welldesigned large population-based studies will validate current findings and provide the rationale for identifying at-risk subpopulations for primary prevention of gastric cancer.