Use of Proton Pump Inhibitors and the Risk for the Development of Gastric Cancers: A Nationwide Population-Based Cohort Study Using Balanced Operational Definitions

SIMPLE SUMMARY: Previous cohort studies using national claim data in Korea have shown conflicting results about the association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer. In this population-based cohort analysis using balanced operational definitions, proton pump inhibitor use was not associated with an increased risk of gastric cancer (Hazard ratio: 1.30, 95% confidence interval: 0.75–2.27). Previous cohort studies with an inappropriate operational definition for the inclusion criteria of the study subjects or index dates could be the reason of conflicting results. ABSTRACT: Objectives: Previous cohort studies using national claim data in Korea have shown conflicting results about the association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer. This may be due to differences in the inclusion criteria or index dates of each study. This study aims to evaluate the association between PPI use and the risk of gastric cancer using balanced operational definitions. Design: A population-based cohort analysis was conducted using the Korean National Health Insurance Service database. Subjects who used PPIs or histamine-2 receptor antagonist (H(2)RA) for more than 60 days after Helicobacter pylori eradication were included. The study subjects were those who had never used H(2)RAs (PPI users) and controls were those who had never used PPIs (H(2)RA users). For comparison, the index dates of previous studies were adopted and analyzed. The subjects were followed until the development of gastric cancer, death, or study end. Results: A total of 10,012 subjects were included after propensity score matching. During a median follow-up of 6.56 years, PPI was not associated with an increased risk of gastric cancer (Hazard ratio: 1.30, 95% confidence interval: 0.75–2.27). This was consistent if the cumulative daily dose was adjusted (90/120/180 days), or if the index date was changed to the first day of PPI prescription or the last day of Helicobacter pylori eradication. There was no significant difference in mortality between both groups. Conclusion: PPI use was not associated with an increased risk of gastric cancer.