Use of proton pump inhibitors and risk of gastric cancer: a systematic review and meta-analysis
Dr. Daniele Piovani MSc, PhD Epidemiologist
I attest that I have no conflict of interests related to this study to disclose
Department of Biomedical Sciences, Humanitas University, Milan, Italy
What is already known on this topic
- Previous observational studies and meta-analyses suggest that exposure to proton-pump inhibitors (PPIs) is associated with increased risk of gastric cancer .
- Several methodological issues and biases may affect this area of research.
- The causal role of PPI use on the development of gastric cancer is still heavily debated in the medical community.
What we did
- Systematic search of Medline/PubMed, Embase and Scopus databases for randomized and observational studies of the association between PPIs and gastric cancer
having considered Histamine-2 receptor antagonists (H2RAs) users as controls
- Stratified analyses and meta-regression were employed to explore heterogeneity.
- We used GRADE to evaluate certainty in the body of evidence.
- 2 randomized clinical trials (498 patients; 1 gastric cancer)
- 12 Observational studies (>6 million patients; 11,554 gastric cancers)
➢ 6 studies provided a comprehensive adjustment of confounding
➢ 3 studies provided partially-adjusted effect estimate
➢ 2 studies provided crude/unadjusted relative risk estimate
➢ 1 study excluded due to population overlap
The 6 observational studies providing comprehensive adjustment of confounding
included about 2.5 million patients receiving either PPIs or H2RAs and 7,372 gastric cancers
❑ Meta-analysis of six observational studies providing a comprehensive adjustment for
confounding did not show any association between PPIs and gastric cancer
( RR random =1.07, 0.97−1.19 ; RR fixed =1.05, 0.98−1.12).
❑ Certainty in the random-effect estimate was low (observational studies) but the results
were consistent across sensitivity analyses .
❑ No convincing evidence of a dose-response, or of increased risk with long-term use
was found.
❑ Lack of or minimal adjustment for confounding was associated with larger effect sizes.
Interpretation:
❑ Patients using PPIs did not show a significantly differential risk of gastric cancer as
compared to those using H2RAs when adjustment of confounding was
comprehensive.
❑ The (nonsignificant) absolute increase corresponded to 2 more cases per 10,000
(from 1 less to 6 more) patients.
IMPLICATIONS FOR PRACTICE Our findings are reassuring to all those patients who have an indication for long-term PPI use and need a persistent and effective acid gastric suppression to prevent serious health consequences.
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