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I read with great interest the recent article by Cheung et al reporting a duration-dependent association between the long-term use proton pump inhibitors (PPI) and an increased risk of gastric cancer in patients, even after Helicobacter pylori (HP) eradication therapy.1 Chronic gastritis due to HP infection induces mutagenesis through deamination and nitration of DNA, via a reaction with inducible nitric oxide synthase (iNOS)-derived NO and superoxide from inflammatory cells.2 However, Cheung et al further demonstrated that continued PPI treatment, even after HP eradication, could also increase the risk for gastric cancer. I support the findings of this paper from the perspective of the importance of physiological acidity in the formation of carcinogenic N-nitroso compounds (NOC) in the stomach.
Gastric …