Pathogenesis of pre-neoplastic lesions of the stomach: targets for prevention

Gastric atrophy and intestinal metaplasia are generally considered to be precancerous lesions of the stomach. Chronic Helicobacter pylori infection is one the most important factors in the development of these pre-malignant gastric lesions. In addition to bacterial factors, polymorphisms in the cytokine genes of the host that modulate inflammatory responses are found to have a synergistic effect in the development of gastric cancer as well as pre-neoplastic lesions. Recently, inappropriate activation of the intestine-specific transcription factor like the homeobox gene complex CDX1 and CDX2 are found to be an important contributing factor in the induction of intestinal metaplasia in the stomach. Aberrant expression of cyclooxygenase-2 and epigenetic changes are also frequently detected in pre-neoplastic gastric lesions. One of the most important questions relating to these pre-neoplastic gastric lesions is that whether H. pylori eradication could reverse these changes. However, most controlled studies showed no or just modest improvement in intestinal metaplasia after H. pylori eradication. Further studies should evaluate the role of other chemopreventive agents, particularly cyclooxygenase-2 inhibitor, on regression of pre-neoplastic lesions.