BACKGROUND - Helicobacter pylori is a bacterial carcinogen that is supposed to have the highest known level of risk for the development of gastric cancer, a disease that claims hundreds of thousands of lives per year. Approximately 89% of the global gastric cancer burden and 5.5% of malignancies worldwide are attributed to H. pylori-induced inflammation and injury. However, only a fraction of colonized persons ever develop neoplasia, and disease risk involves well-choreographed interactions between pathogen and host, which are dependent upon strain-specific bacterial factors, host genotypic traits, and/or environmental conditions.
KEY MESSAGES - One H. pylori strain-specific virulence determinant that augments the risk for gastric cancer is the cag pathogenicity island, a secretion system that injects the bacterial oncoprotein CagA into host cells. Host polymorphisms within genes that regulate immunity and oncogenesis also heighten the risk for gastric cancer, in conjunction with H. pylori strain-specific constituents. Further, conditions such as iron deficiency and high salt intake can influence H. pylori phenotypes that lower the threshold for disease.
CONCLUSIONS - Delineation of bacterial, host, and environmental mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer, but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.
© 2016 S. Karger AG, Basel.