Meta-analysis: No link between PPI use and gastric cancer

Proton pump inhibitor (PPI) therapy does not appear to put individuals who require gastric acid suppression at increased risk of gastric cancer, according to a study.

Researchers performed a systematic review and meta-analysis of studies evaluating the association between PPIs and the risk of gastric cancer. They searched multiple online databases for randomized and nonrandomized studies (NRS) involving PPI users and histamine-2 receptor antagonists (H2RAs) users as controls. This comparison was made to minimize confounding by indication and focus on patients requiring gastric acid suppression.

Heterogeneity and small-study effect were assessed, and summary estimates were calculated using random- and fixed-effect models. Stratified analyses and meta-regression were used to explore heterogeneity.

The initial search yielded 8,375 records, of which 12 NRS (>6 million patients; 11,554 gastric cancer cases) and two randomized clinical trials (RCTs; 498 patients; one gastric cancer case) met the eligibility criteria. Evidence from RCTs was very imprecise and provided very-low certainty evidence.

Pooled data from six NRS (2.5 million patients; 7,372 gastric cancer cases) did not show any association between PPIs and gastric cancer (relative risk [RR]_random, 1.07, 95 percent confidence interval [CI], 0.97–1.19; RR_fixed, 1.05, 95 percent CI, 0.98–1.12). Evidence certainty was low.

There was no evidence of dose–response associations or increased risk of gastric cancer with long-term PPI use. Lack of or minimal adjustment for confounding yielded larger effect sizes.