No evidence of link between proton pump inhibitors and gastric cancer

Findings

• Current evidence suggests that taking proton pump inhibitors (PPIs) is not correlated with an increased risk of gastric cancer.
• For physicians considering discontinuing PPI treatment, the authors advise the same approach as in the recent proposal by the American Gastroenterological Association: to check whether there is an indication for use, not whether side effects are to be feared.

Why this matters

• PPIs are among the most commonly prescribed drugs in the world.
• Gastric cancer is the fourth leading cause of cancer-related death worldwide.
• Some previous evidence suggested that PPIs may increase cancer risk and are associated with: 
  • cell proliferation
  • Atrophy of the stomach
  • Change in gut microbiota
  • Change in mucosal immune response
• This meta-analysis was the first to focus on studies with an active control group (patients taking histamine-2 receptor antagonists [ H2RAs].

• cell proliferation
• Atrophy of the stomach
• Change in gut microbiota
• Change in mucosal immune response

Study design

• Systematic review and meta-analysis of 12 non-randomized trials (n> 6  millions) and 2 randomized trials (n = 498) investigating the association between PPIs and gastric cancer
• The studies compared PPI users with H2RA users.
  • This reduced the risk of confounding factors caused by the indication.
  • Both groups may have a similar risk of cancer at baseline due to underlying stomach problems.
• Result: Gastric carcinoma
• Funding: Bibliosan financed the open access publication.

• This reduced the risk of confounding factors caused by the indication.
• Both groups may have a similar risk of cancer at baseline due to underlying stomach problems.

Key findings

• Gastric cancer cases:
  • in non-randomized trials: 11,554
  • in randomized trials: 1
• In a meta-analysis of 6 non-randomized trials with the highest quality evidence (n = 2,5  millions), no significant association was observed between PPI use and gastric cancer (low safety).
• There was no evidence of a dose-response effect.
• There was no evidence of stronger effects with long-term PPI use.
• When considering studies with lower quality evidence, there appeared to be a higher risk of cancer, but with very little certainty or very low reliability.

• in non-randomized trials: 11,554
• in randomized trials: 1

Restrictions

• The vast majority of patients participated in non-randomized trials, not randomized trials.
• H2RAs could potentially also increase the risk of cancer.
• The evidence from the studies was of low quality.
• Risk of remaining confounding factors

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