Perspectives on gastric cancer: the central role of gastrin in carcinogenesis by Helicobacter pylori, oxyntic atrophy and drug-induced acid suppression
Abstract
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.
Read the paper
Related studies
- The Prediction of the In Vitro Release Curves for PLGA-Based Drug Delivery Systems with Neural Networks
- Promising Ursolic Acid as a Novel Antituberculosis Agent: Current Progress and Challenges
- Proof of principle concept for the analysis and functional prediction of rare genetic variants in the CYP2C19 and CYP2D6 genes
- Fabrication, characterization, and docking studies of furosemide-loaded nanosponges using the emulsion solvent diffusion method
- The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter-Mediated Drug–Drug Interactions
- Mining the Metabolic Capacity of Clostridium sporogenes Aided by Machine Learning
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.