Antiulcer drugs and gastric cancer.

Inhibitors of gastric acid secretion are efficient drugs in the treatment of acid-related diseases. However, by reducing gastric acidity, hypergastrinemia develops. Gastrin regulates its target cell, the enterochromaffin (ECL) cell, both functionally and tropicaly. Long-term hypergastrinemia in whatever species studied, has been shown to induce tumors originating from the ECL cell. In man, at least 10 years of hypergastrinemia, accompanied by high or reduced gastric acidity is necessary to induce ECL cell carcinoids. There are reports indicating development of ECL cell carcinoids after long-term treatment with proton pump inhibitors. Moreover, the ECL cell may give rise to gastric carcinomas of diffuse type, which have increased during the last decades. Furthermore, most of the carcinomas developing in patients with long-lasting hypergastrinemia are of ECL cell origin. Therefore, long-lasting iatrogenic hypergastrinemia induced by potent inhibitors of acid secretion may be expected to increase the occurrence of gastric carcinomas in the future.