REVIEW ARTICLE - PATHOGENESIS OF THE TRANSFORMATION FROM GASTRITIS TOMALIGNANCY

Helicobacter pylori acquisition is the main cause of chronic gastritis in humans, In up to half of the infected subjects, chronic gastritis progresses to atrophic gastritis and intestinal metaplasia. During thi s course, various mechanisms are triggered that may contribute to the pathogenesis of gastric cancer. Such mechanisms include the inflammati on-related cascades of cytokine and free radical reactions, up-and dow nregulation of growth factors and their receptors, and the atrophy-rel ated impairment of acid output and intraluminal acidity. An array of o ther factors may also have become significant including overgrowth of bacteria other than H. pylori in the hypochlorhydric or achlorhydric s tomach, a high dietary consumption of salt, nitrate, or nitrite, smoki ng, deficiency of vitamins or micronutrients, influence of sex hormone s, or an inherited liability of the dividing epithelial cells to gene errors. These factors may vary in effect between populations and indiv iduals but, if active, may affect the cell genome which may further in fluence the course and progression of chronic gastritis, and can final ly result in overt gastric neoplasia. The molecular biology of gastric cancer has revealed a spectrum of gene errors which vary in type and extent between different histological types of cancer, and between ind ividual cases. There now is evidence that the intestinal metaplasia or the gastric epithelium in atrophic gastritis reveal signs of abnormal expression of various regulatory genes well before the appearance of gastric neoplasia. It is possible that the mechanisms leading to mutat ion of the genes in epithelial cells are triggered very early in the H . pylori gastritis cascade, and that atrophic gastritis and intestinal metaplasia result from these processes.