Long-Term PPI Use Does Not Increase Gastric Cancer Risk: BMJ | 2026
Introduction:
Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Concerns have persisted that long-term acid suppression, through hypochlorhydria and hypergastrinemia, might increase gastric cancer risk. This large Nordic population-based study examined whether long-term PPI exposure is associated with non-cardia gastric adenocarcinoma.
Why was this study needed?
Previous observational studies reported conflicting associations between PPIs and gastric cancer.
H. pylori infection, peptic ulcer disease, and protopathic bias can substantially confound these associations.
Gastric carcinogenesis has a long latency, requiring prolonged follow-up.
Reliable evidence is important because inappropriate fear of cancer may lead to unnecessary PPI discontinuation.
Results:
The analysis included 17,232 gastric cancer cases and 172,297 matched controls across five Nordic countries.
After adjustment for important confounders, long-term PPI use was not associated with gastric cancer (adjusted OR 1.01).
H2-receptor antagonists similarly showed no increased risk.
Importantly, alternative analyses using shorter lag periods or inadequate adjustment produced apparently positive associations—demonstrating how methodological bias can create a false PPI–cancer signal.
Clinical Impact:
This large study provides reassuring evidence that appropriate long-term PPI therapy should not be discontinued because of fear of gastric cancer. PPIs should still be reviewed periodically and deprescribed when there is no continuing indication, but decisions should be based on clinical necessity rather than unsupported cancer concerns.
Bottom Line:
Long-term PPI use was not associated with increased gastric adenocarcinoma risk after appropriate adjustment for confounding. The practical message is reassuring: prescribe PPIs when indicated, review the indication periodically, and do not deprescribe solely because of fear of gastric cancer.
