Association between proton pump inhibitor use and upper gastrointestinal cancer: A matched case-control study accounting for reverse causation and confounding by indication

Apparent harmful associations between PPI use and upper GI cancer were concentrated in the months immediately preceding diagnosis and disappeared after adjusting for diagnostic context and excluding the final year before diagnosis. In these adjusted analyses, we found no evidence of increased odds with long-term PPI use, and remote use (>3 years before diagnosis) was associated with reduced cancer odds for omeprazole and lansoprazole. These findings underscore the importance of investigating new-onset upper GI symptoms rather than attributing malignancy risk to acid-suppressive therapy.