Gastric carcinoma: failed adaptation to Helicobacter pylori

Helicobacter pylori is the major cause of chronic gastritis. Unlike bacterial infections in general, H. pylori acquisition causes a chronic, usually life-long infection. After acquisition, chronic inflammation (gastritis) appears and develops slowly into atrophic gastritis (with intestinal metaplasia) in a proportion of affected subjects. Inflammation and atrophy result from a failure of the immune system to eliminate the H. pylori infection. In infected stomach, several cascades of reactions are triggered which may result in impairments of structure and function of the gastric mucosa, some of which lesions also increase the risk of gastric carcinoma (CGA). A sequence of events from an early H. pylori infection into an atrophic gastritis has risen a theory that the H. pylori acquisition is a key issue in the development of GCA. Several aspects in the epidemiology and pathogenesis of GCA can be understood and explained by this infectious background. The H. pylori gastritis is unexpectedly common in patients with GCA of both intestinal or diffuse type, and the infection and gastritis precede the development of cancer. In Finland, 70-80% of the GCA cases seem to develop in connection with an H. pylori-positive gastritis or atrophy, 10-15% develop in a normal stomach (genetically determined GCA cases?), and 10-15% are associated with an H. pylori-negative corpus-limited (autoimmune) gastritis and atrophy. Case control studies suggest that the presence of H. pylori related inflammation raises the risk of GCA twofold, and the appearance of atrophic gastritis (and intestinal metaplasia) raises further this risk 2-3 times, as compared to the risk of GCA in subjects with a normal stomach.