Therapeutic achlorhydria and risk of gastric cancer.

New, powerful gastric secretory inhibitors, such as omeprazole, produce gastric cancer in rats. The mechanism by which the drugs elicit gastric carcinogenesis is considered to depend on the production of therapeutic achlorhydria, with subsequent release in to the circulation of peptides (such as gastrin) which are trophic to the gastric mucosa. It has been argued that the drugs do not pose a carcinogenic risk to man because the neoplastic response to gastric inhibitors in rats is a reaction to a 'toxic' insult; or because rats and humans react differently to the drugs; or because the mechanisms of gastric carcinogenesis are different in the two species. In any case, since most of the powerful gastric secretory inhibitors produce carcinoid tumours in rats, and carcinoid tumours of the human stomach are rare and largely benign, there would be no risk even if the drugs did produce proliferative abnormalities of the human stomach. Not one of the above hypotheses has been confirmed or, indeed, even satisfactorily tested. The mechanisms of the drug-induced gastric carcinogenesis in rats has not been defined and consequently it is not even possible to attempt to guess the risk to man. Until information is available about the effects of the powerful gastric secretory inhibitors on the proliferative indices and patterns of the human gastric mucosa, the drugs must be categorized as too dangerous to use therapeutically, especially since the proposed therapeutic benefits are minimal.