Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis

Clin Gastroenterol Hepatol. 2016 Dec;14(12):1706-1719.e5. doi: 10.1016/j.cgh.2016.05.018. Epub 2016 May 20.


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.

Keywords: Acid-Suppressive Drug; Neoplasm; Side Effect; Stomach Carcinoma.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Humans
  • Observational Studies as Topic
  • Polyps / chemically induced*
  • Polyps / epidemiology*
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Stomach Neoplasms / chemically induced*
  • Stomach Neoplasms / epidemiology*


  • Proton Pump Inhibitors

Supplementary concepts

  • Polyposis Of Gastric Fundus Without Polyposis Coli