Population-based case-control study of long-term use of proton pump inhibitors and risk of stomach cancer in five Nordic countries

The association between use of proton pump inhibitors (PPIs) and risk of stomach cancer is not clear. A population-based case-control study in Denmark, Finland, Iceland, Norway, and Sweden investigated the association of long-term use of PPIs with risk of gastric non-cardia adenocarcinoma. Case patients with gastric non-cardia adenocarcinoma (n=17,232) were each matched for age, sex, calender year, and country with 10 control participants randomly identified from each country’s entire population (n=172,297). Long-term PPI use was observed in 1766 (10.2%) cases and 16,312 (9.5%) controls (adjusted OR 1.01; 95% CI 0.96-1.07). The risk was similar for histamine-2-receptor antagonist use (aOR 1.03; 95% CI 0.86-1.23). Multiple sources of error that led to a false positive association were identified – inclusion of PPR use shortly before gastric adenocarcinoma diagnosis, short-term use of PPIs, cardia adenocarcinoma, and lack of adjustment for Helicobacter pylori related variables. The authors conclude that long term PPI use may not be associated with an increased risk of gastric adenocarcinoma.