Use of Proton Pump Inhibitors vs Histamine 2 Receptor Antagonists for the Risk of Gastric Cancer: Population-Based Cohort Study

INTRODUCTION:Proton pump inhibitors (PPIs) are commonly prescribed medications. Long-term use of PPIs has been suspected to have a provocative effect on gastric cancer. This study was to determine the association between PPI vs histamine 2 receptor antagonist (H₂RA) use and the risk of gastric cancer in a region where the risk of this malignancy is high.METHODS:A population-based cohort study using the Korean National Health Insurance Services Database. The participants with first prescription of PPIs and H₂RA with normal esophagogastroduodenoscopy finding from 2004 through 2015 were collected. Among them, 50% of participants were systematic stratified randomly sampled. There were 122,118 users of PPIs or H₂RAs who use medication more than cumulative defined daily dose of 180 days. The users were followed up from long-term use threshold until gastric cancer, death from non-gastric cancer cause, gastric surgery, or study end (December 2017).RESULTS:After calculating propensity score weights, we included 39,799 PPI and 38,967 H₂RA users. Among the new PPI and H₂RA users, we identified 411 cases of incident gastric cancer from 182,643 person-years of follow-up observation and 397 cases from 178,846 person-years of follow-up observation, respectively. Compared with H₂RA users, PPI users did not experience significantly different gastric cancer incidence (adjusted hazard ratio, 1.01; 95% confidence interval, 0.88-1.16; P = 0.89). Sensitivity analyses confirmed that gastric cancer incidence did not differ between PPI and H₂RA users.DISCUSSION:In this large study, long-term treatment with PPIs vs H₂RAs did not show higher risk of gastric cancer even in a high-risk region.