Perspectives on gastric cancer: the central role of gastrin in carcinogenesis by Helicobacter pylori, oxyntic atrophy and drug-induced acid suppression

Background: The function of the acid production in the upper gastrointestinal tract is to kill swallowed microorganisms and has been preserved in development since primitive fishes. However, acid production contributes to peptic ulcers and reflux esophagitis. Main body: Gastric acidity is sensed by the G cell producing gastrin, which regulates release of mediators from and proliferation of the enterochromaffin like (ECL) cell. Drugs inhibiting gastric acidity profoundly induce hypergastrinemia and were early shown to cause malignant tumors in rodents. In humans these drugs also lead to hypergastrinemia and ECL cell hyperplasia, but tumors have not been reported until more recently. Tumor latency depends on the natural life length of a species. H. pylori, the main cause of gastritis, peptic ulcer disease and gastric cancer, was early accepted as a carcinogen by WHO. However, no direct carcinogen was found and subsequently H. pylori carcinogenesis was shown to depend on development of oxyntic atrophy which is not compatible with being a direct carcinogen. H. pylori and autoimmunity are the main causes of oxyntic atrophy, hypoacidity, hypergastrinemia and gastric cancer. Conclusions: Gastrin is central in gastric carcinogenesis. H. pylori is the dominating cause of gastric cancer of both intestinal and diffuse types and H. pylori carcinogenesis may be explained by hypergastrinemia. A gastrin antagonist is long-awaited.