Helicobacter pylori and Gastric Cancer

Epidemiological studies have determined that the attributable risk for gastric cancer conferred by Helicobacter pylori is approximately 75 %. 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. These observations in conjunction with recent evidence that carriage of certain strains is inversely related to esophageal adenocarcinoma and atopic diseases, underscore the importance of understanding mechanisms that regulate biological interactions of H. pylori with their hosts that promote carcinogenesis. H. pylori strains are extremely diverse, freely recombining as panmictic populations. One strain-specific virulence determinant that augments the risk for gastric cancer is the cag pathogenicity island, a type 4 secretion system that injects the bacterial oncoprotein CagA into host epithelial cells. The use of broad-range 16S rRNA PCR coupled with high throughput sequencing has demonstrated that H. pylori does not simply exist as a monoculture within the human stomach but instead, is a resident of a distinct gastric microbial ecosystem. While H. pylori is the dominant species, the presence of other microorganisms provides a genetic repository which may facilitate the generation of novel traits that influence gastric carcinogenesis. Host polymorphisms within genes that regulate immunity (e.g., IL-1[beta]) and oncogenesis (e.g., mmp-7) also heighten the risk for gastric cancer, in conjunction with H. pylori strain-specific constituents. Further, environmental conditions such as iron deficiency and high salt intake can influence H. pylori phenotypes that lower the threshold for disease. 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.