J Neurogastroenterol Motil.  2025 Apr;31(2):178-185. 10.5056/jnm24145.

Association of Proton Pump Inhibitor Use With Gastric Cancer in Regions With High Prevalence of Gastric Cancer: Systematic Review and Meta-analysis

• Kang SJ
• Lee KJ

• KMID: 2567119
• DOI: http://doi.org/10.5056/jnm24145

Abstract

Background/Aims
Although the association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer has been postulated in casecontrol and cohort studies, it remains still controversial. We aim to evaluate association of PPI use with gastric cancer in regions with high prevalence of gastric cancer, particularly in patients who underwent eradication of Helicobacter pylori, by systemic review and meta-analysis.
Methods
Comprehensive literature search through the PubMed, Embase, and Cochrane database was performed in October 2023. We used random effects model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) between PPI use and gastric cancer. The Cochran Q-statistic and the I² test were employed for evaluating potential heterogeneity between studies.
Results
Two case-control and 6 cohort studies were identified. PPI use was significantly associated with the development of gastric cancer (OR, 2.02; 95% CI, 1.35-3.01). In subgroup analysis carried out according to the study design, sample size, and adjustment of confounding factors (age, sex, and H. pylori), such association was significant. A meta-analysis of 4 studies performed in patients with H. pylori eradication history showed that the use of PPIs was significantly associated with an elevated incidence of gastric cancer (OR, 2.10; 95% CI, 1.48-2.97).
Conclusions
Long-term use of PPIs is associated with an increased risk of gastric cancer in Asian regions with high prevalence of gastric cancer, particularly in subjects who have eradication history of H. pylori. Optimization of long-term PPI use seems to be necessary in regions where gastric cancer is prevalent.

Keyword

Gastric cancer; Helicobacter pylori; Meta-analysis; Proton pump inhibitors