At the bedside: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer

Abstract

Clinical trials performed in populations at high GC risk have demonstrated that eradication of Helicobacter pylori from the stomach with a course of combination antimicrobials helps prevent gastric carcinogenesis when they are administered before precancerous lesions have yet developed. In this review, we consider the insights into H. pylori-associated gastric carcinogenesis that have been gained from these and many other clinical studies in the field to highlight priority areas for basic research and clinical investigation. Among these are defining the magnitude of the risk reduction that may be achieved in clinical practice and at a population level by H. pylori eradication and investigating when, during the slow multistep progression to GC, intervention will be of the most benefit. Additional strategies to prevent GC induced by H. pylori, including chemoprevention, dietary modification, and close endoscopic surveillance, may also have value in augmenting the risk reduction. Why only a small subpopulation of those infected by H. pylori go on to develop GC may be partially explained by genetic susceptibility related to SNPs in several genes regulating the intensity of the gastric inflammatory response to H. pylori. Investigation of the basic mechanisms underlying the promotion of GC by H. pylori and the associated inflammatory response will likely continue to improve clinical strategies for the prevention of one of the most common causes of cancer death globally. See related review, At the Bench: H. pylori, dysregulated host responses, DNA damage, and gastric cancer.

Keywords: chemoprevention; eradication therapy; gastric carcinogenesis; intestinal metaplasia; single nucleotide polymorphisms.

Figure 1.. Diverse outcomes of H. pylori infection.

H. pylori causes chronic gastritis, which in the vast majority of infected patients, results in no clinical effects. Approximately 20% of patients develops peptic ulcers, dyspeptic symptoms, or rarely, gastric lymphoma. Fewer than 2% of those infected by H. pylori worldwide develop GC. The most common pathway to GC progresses along the Correa cascade (atrophic gastritis, IM, dysplasia) to intestinal-type GC, although H. pylori is also associated with the development of diffuse-type GC via a molecular/histological path that remains relatively poorly defined.