Chronic gastritis induced by Helicobacter pylori (H. pylori) is the strongest known risk factor for adenocarcinoma of the distal stomach, yet the effects of bacterial eradication on carcinogenesis remain unclear. H. pylori isolates possess substantial genotypic diversity, which engenders differential host inflammatory responses that influence clinical outcome. H. pylori strains that possess the cag pathogenicity island and secrete a functional cytotoxin induce more severe gastric injury and further augment the risk for developing distal gastric cancer. Carcinogenesis is also influenced by host genetic diversity, particularly involving immune response genes such as interleukin-1β and tumor necrosis factor-α. Human trials and animal studies have indicated that eradication of H. pylori prior to the development of atrophic gastritis offers the best chance for prevention of gastric cancer. However, although the timing of intervention influences the magnitude of suppression of premalignant and neoplastic lesions, bacterial eradication, even in longstanding infections, is of clear benefit to the host. It is important to gain insight into the pathogenesis of H. pylori-induced gastritis and adenocarcinoma not only to develop more effective treatments for gastric cancer, but also because it might serve as a paradigm for the role of chronic inflammation in the genesis of other malignancies that arise within the gastrointestinal tract.
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