Long-term proton pump inhibitor (PPI) use may not be associated with an increased risk of gastric adenocarcinoma, according to findings from a Nordic health study published by Duru et al The BMJ.
According to the report's authors, “This finding should offer relief for patients needing long-term PPI therapy and is valuable for health care in clinical decision-making.”
Background and Study Methods
Researchers conducted a population-based case-control study of prospectively collected data from between 1994 and 2000 from multiple nationwide registries from Denmark, Finland, Iceland, Norway, and Sweden. The study assessed 17,232 cases of patients with gastric noncardia adenocarcinoma and 172,297 case controls matched for age, sex, calendar year, and country. Gastric cardia adenocarcinoma was excluded to avoid confounding factors.
For the study, long-term PPI use was defined as more than a year, excluding the year before the diagnosis date for patients with gastric cancer or the inclusion date for case controls. The validity and specificity of PPI use was also assessed by looking at long term use of histamine-2-receptor antagonists.
Key Findings
Among the patient cases, 10.2% had long-term exposure to PPIs, along with 9.5% of controls. No association was identified between long-term PPI use and gastric adenocarcinoma (adjusted odds ratio [aOR] = 1.01; 95% confidence interval [CI] = 0.96–1.07). There was also no association between risk for gastric adenocarcinoma and long-term histamine-2-receptor antagonist use (aOR = 1.03; 95% CI = 0.86–1.23).
The researchers identified multiple sources of error leading to a false-positive association, including PPI use shortly before being diagnosed with gastric adenocarcinoma, short-term PPI use, cardia adenocarcinoma, and lack of adjustment for Helicobacter pylori.
The study authors noted, however, that as this was an observational study, no definitive conclusions can be drawn about the relationship between gastric adenocarcinoma and long-term PPI use. As such, they noted the possibility that factors such as diet and family history of stomach cancer that were not assessed in this study could have affected the results, though they did also acknowledge that the multinational study allowed them to mitigate many biases affecting prior research on this topic.
DISCLOSURE: The study authors declared support from the Swedish Research Council, Nordic Cancer Union, and Swedish Cancer Society for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
