Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Daniel Segna; Nele Brusselaers; Damian Glaus; Niklas Krupka; Benjamin Misselwitz

doi:10.1177/17562848211051463

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Therap Adv Gastroenterol. 2021 Nov 10:14:17562848211051463. doi: 10.1177/17562848211051463. eCollection 2021.

Authors

Daniel Segna¹, Nele Brusselaers², Damian Glaus³, Niklas Krupka⁴, Benjamin Misselwitz⁴

Affiliations

¹ Hepatology, Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Freiburgstrasse 4, 8010 Bern, Switzerland.
² Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
³ Faculty of Medicine, University of Zurich, Zurich, Switzerland.
⁴ Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland.

Abstract

Introduction: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC).

Objective: To review and meta-analyse available literature investigating the association between PPI use and GC risk.

Methods: Two independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1-3 years, >3 years).

Results: We screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47-2.56] with high statistical heterogeneity (I ² = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44-3.36, I ² = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72-4.36, I ² = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13-2.47, I ² = 0%; 1-3 years: OR: 1.46, 95% CI: 0.53-4.01, I ² = 35%; >3 years: OR: 2.08, 95% CI: 0.56-7.77, I ² = 61%).

Conclusion: We found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.

Keywords: meta-analysis; proton-pump inhibitors; stomach neoplasms; systematic review.