Proton Pump Inhibitors and Gastric Cancer: A Large-Scale Propensity Score-Matched Analysis

We aimed to elucidate whether proton pump inhibitor (PPI) users are at increased risk of gastric cancer compared with non-PPI users or histamine-2 receptor antagonist (H2RA) users.

A population-based cohort study was conducted using data from the UK Biobank from 1990 to 2016. We compared the incidence of gastric cancer after a minimum of 1-year drug exposure between PPI users and non-PPI or H2RA users using Cox proportional hazards models. Secondary analyses assessed the duration and dose-response associations. Sensitivity analyses incorporating various matching ratios, extended lag periods, and propensity score stratification were performed.

After large-scale propensity score matching, we included 42,732 new PPI users, 42,732 non-PPI users, and 4,762 new H2RA users. During a median follow-up of 6.7 years, PPI users had a 2.32-fold higher risk of gastric cancer than non-PPI users (hazard ratio [HR], 2.324; 95% confidence interval [CI], 1.646 to 3.282), with numbers needed to harm of 488 and 442 at 2 and 4 years, respectively. Compared with H2RA users, PPI users also had a significantly higher incidence of gastric cancer (HR, 5.343; 95% CI, 1.557 to 18.335). The risk of gastric cancer tended to increase with a longer cumulative duration of PPI use and higher cumulative doses of PPIs. Moreover, these results remained robust after adjustments for various lag periods, matching ratios, and propensity score stratification.

PPI use was associated with a higher incidence of gastric cancer, albeit with a low absolute risk. Therefore, long-term PPI use should be considered cautiously, even in regions with a low risk of gastric cancer.