Association between use of acid-suppressive drugs and risk of gastric cancer. A nested case-control study

Drug Saf. 2008;31(8):675-84. doi: 10.2165/00002018-200831080-00004.


Background: The risk of gastric cancer could be influenced by acid-related diseases or by the use of acid-suppressive drugs, such as histamine H(2) receptor antagonists and proton pump inhibitors (PPIs).

Objective: To assess the association between exposure to acid-suppressive drugs and the risk of gastric cancer.

Methods: A nested case-control study was conducted among people registered in the Quebec health insurance plan (Canada). Cases represented a random sample of subjects diagnosed with gastric cancer between 1995 and 2003 who were matched on age and sex to at least four controls (using incidence density sampling). The index date was the date of cancer diagnosis for the cases, which was the index date for the matched controls. The exposure definition in the 5 years preceding the index date was based on the defined daily doses of acid-suppressive drugs and categorized into quartiles.

Results: The study included 1598 gastric cancer cases and 12 991 controls. The adjusted odds ratios for the association between exposure to acid-suppressive drugs and risk of gastric cancer were 1.47 (95% CI 1.23, 1.76), 1.32 (95% CI 1.10, 1.58), 1.48 (95% CI 1.24, 1.77) and 1.18 (95% CI 0.97, 1.44) for the first, second, third and fourth exposure quartiles, respectively. Similar results were obtained when use of H(2) receptor antagonists and PPIs were assessed separately (odds ratios for the association between PPIs and the risk of gastric cancer were slightly higher compared with H(2) receptor antagonists and risk of gastric cancer).

Conclusions: A minor increase in the risk of gastric cancer was observed if exposure to either H(2) receptor antagonists or PPIs occurred within the past 5 years. However, this association is probably not causal since it is most likely due to confounding by indication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Ulcer Agents / adverse effects*
  • Case-Control Studies
  • Female
  • Gastric Acid / metabolism
  • Histamine H2 Antagonists / adverse effects*
  • Humans
  • Male
  • Odds Ratio
  • Proton Pump Inhibitors / adverse effects*
  • Quebec / epidemiology
  • Risk
  • Stomach Neoplasms / chemically induced*
  • Stomach Neoplasms / epidemiology
  • Time Factors


  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors