The effect of prior proton pump inhibitor use on gastric cancer survival: A population-based cohort study in the five Nordic countries

OBJECTIVES: Proton pump inhibitors (PPI) might mask gastric cancer symptoms, leading to delayed diagnosis and worse oncological outcomes. However, current evidence is sparse and underpowered. This study aimed to elucidate if PPI-use influences oncological outcomes of gastric cancer in a well-powered study. METHODS: This population-based cohort study included individuals with gastric non-cardia adenocarcinoma from the five Nordic nations. Multiple nationwide registries provided prospectively collected data. The individuals were grouped into non-users, light users, or heavy PPI-users during the 2-year period before diagnosis. The outcomes 5-year disease-specific mortality (primary) and 5-year all-cause mortality were analyzed using Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI). The outcomes metastatic disease and advanced tumor stage at diagnosis were analyzed using logistic regression, providing odds ratios (OR) with 95% CI. The risk estimates were adjusted for age, sex, country, year, comorbidity, and Helicobacter pylori treatment. RESULTS: Among 21,433 individuals with gastric non-cardia adenocarcinoma, there were 9,736 users and 11,697 non-users. Heavy and light PPI use were both associated with reduced risk of 5-year disease-specific mortality (adjusted HR=0.90, 95% CI 0.86-0.94 and HR=0.87, 95% CI 0.84-0.91, respectively), with similar results for 5-year all-cause mortality. Heavy PPI-use was associated with decreased risks of presenting with metastatic disease (adjusted OR=0.70, 95% CI 0.64-0.76) or advanced tumor stage (adjusted OR=0.71, 95% CI 0.56-0.89). CONCLUSION: PPI-use before gastric non-cardia adenocarcinoma diagnosis may not be associated with an increased risk of advanced disease at presentation or of increased mortality.