Original article
Systematic reviews and meta-analyses
Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis

https://doi.org/10.1016/j.cgh.2016.05.018Get rights and content

Background & Aims

There have been increasing numbers of case reports and observational studies of adverse events in patients receiving long-term therapy with proton pump inhibitors (PPIs). The effects of PPI therapy on risks of fundic gland polyps (FGPs) and gastric cancer have received considerable attention. We performed a systematic review with a meta-analysis of randomized controlled trials and observational studies that assessed these risks.

Methods

We searched the PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials databases for relevant studies published through July 2015. We calculated pooled odds ratio for FGPs and the risk ratio for gastric cancer in PPI users compared with PPI nonusers using fixed- and random-effects models.

Results

We analyzed data from 12 studies, comprising more than 87,324 patients: 1 randomized controlled trial reporting the effect of PPIs on gastric polyps (location not specified), 6 cohort and 1 case-control studies on FGPs, and 1 cohort and 3 case-control studies on gastric cancer. Pooled odds ratios for FGPs were 1.43 (95% confidence interval, 1.24–1.64) and 2.45 (95% confidence interval, 1.24–4.83) from fixed- and random-effects models, respectively. The pooled risk ratio for gastric cancer was 1.43 (95% confidence interval, 1.23–1.66) from each model. We observed significant heterogeneity among studies reporting on FGPs, but not among studies reporting on gastric cancer.

Conclusions

Based on a systematic review with meta-analysis, long-term use of PPIs (≥12 months) is associated with an increased risk of FGPs. PPI therapy might also increase the risk of gastric cancer, but this association could be biased, because of the limited number of studies and possible confounding factors.

Section snippets

Search Strategy and Eligibility Criteria

We searched PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials to identify all English-language studies published from the inception until July 31, 2015 that assessed the association between PPI use and the risk of FGPs or gastric cancer. We used the search terms “proton pump inhibitor,” “omeprazole,” “esomeprazole,” “pantoprazole,” “lansoprazole,” “dexlansoprazole,” “rabeprazole,” “fundic gland polyps,” “fundus polyps” “gastric polyps,” “stomach polyps,” “gastric cancer,”

Results

Figure 1 shows the flow chart of the selection of studies. The search identified 1809 studies. After screening the titles, abstracts, and full text, 12 studies were considered eligible for complete data extraction. Of these, 1 RCT37 reported on the effect on gastric polyps (location not specified), 6 cohort38, 39, 40, 41, 42, 43 and 1 case-control studies44 reported on FGPs, and 1 cohort45 and 3 case-control studies46, 47, 48 reported on gastric cancer. Table 1 shows characteristics of the

Proton Pump Inhibitor Use and Risk of Gastric Polyps

The summary effect and its 95% CI based on the estimates from 1 RCT and 7 observational studies showed that the use of PPIs was associated with an increased risk of FGPs. The likelihood of this association was strengthened by the fact that the pooled OR and its lower bound of the 95% CI from studies with higher quality were much larger than those from studies with lower quality and from all studies. However, the magnitude of the mean effect size remains unclear. Of the 8 included studies, only 3

Conclusions

Long-term use of PPIs (≥12 months) is most likely associated with an increased risk of FGPs, but the clinical significance of this is currently unclear. Therapy with PPIs may also increase the risk of gastric cancer, but this association can be biased because of a limited number of available studies and possible confounding by indication and by other factors. Given the large number of patients receiving PPIs, more and higher quality studies are needed to confirm or repudiate any causal link

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    Conflicts of interest The authors disclose no conflicts.

    Funding This study was supported by The Netherlands Organization for Health Research and Development (ZonMw; Rational Pharmacotherapy Program; Project number 836021018).

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