Intake of Proton-Pump Inhibitors and Gastric Cancer Within the Stomach cancer Pooling (StoP) Project

Background: A potential association between proton-pump inhibitors (PPIs) and gastric cancer (GC) remains undefined. Thus, we aimed to evaluate such association within the Stomach cancer Pooling (StoP) Project. Methods: Data from five case-control studies of the StoP Project were included (1,889 cases, 6,517 controls). We assessed the impact of different exposure definitions, specifically any reported use of PPIs and exposure definitions based on the duration of PPI intake. Additionally, we modelled the dose-response relationship between cumulative duration of PPI intake and GC. Results: Significant associations between PPI intake and GC, both overall and in the stratified analyses, were limited to exposure definitions based on short durations of intake. The overall OR for any reported PPI intake was 1.78 (95% CI: 0.76, 4.14). In the dose-response analysis, the ORs of GC were found to be higher for short durations of PPI intake (six months: OR 3.26 [95% CI: 2.40, 4.42], one year: OR 2.14 [95% CI: 1.69, 2.70], two years: OR 1.50 [95% CI: 1.22, 1.85], three years: OR 1.27 [95% CI: 1.03, 1.56]), with the association becoming not significant for durations longer than three years. Conclusions: Our findings suggest that the observed association between PPIs and GC might be mainly due to reverse causality. Impact: The results of this study suggest that PPIs are a safe therapeutic choice regarding their effect on the occurrence of GC.