Proton Pump Inhibitor Use and Its Association with Lung Cancer Likelihood and Mortality: A Nationwide Nested Case-Control Study in Korea

Background/Objectives: Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders, but their potential association with lung cancer risk and mortality remains underexplored and debated. This study sought to investigate the association between PPI use and lung cancer likelihood and mortality, focusing on the impact of PPI exposure history and duration. Methods: This study utilized data from 6795 lung cancer patients, 27,180 matched controls, and 4257 deceased and 2538 surviving lung cancer patients from the Korean National Health Insurance Service's Health Screening Cohort (2002-2019). Propensity score overlap weighting and logistic regression models were applied to assess the correlations between PPI usage history and duration with lung cancer risk and mortality, while standardized differences ensured balanced baseline characteristics. Results: Overall, PPI use was modestly associated, with a 19% increased likelihood of lung cancer occurrence (95% confidence intervals (CI): 1.12-1.26). Interestingly, prolonged PPI use (>= 30 days) was linked to a 13% reduction in lung cancer incidence (95% CI: 0.80-0.94), particularly in subgroups such as older adults (>= 70 years), individuals with gastroesophageal reflux disease (GERD) or hypertension, and those with low alcohol consumption. Conversely, overall PPI usage was linked with a 36% increased mortality likelihood among lung cancer patients (95% CI: 1.20-1.55), with prolonged use further correlating with a 27% higher mortality risk (95% CI: 1.05-1.53), especially in high-risk subgroups, including smokers, underweight individuals, and those with hypercholesterolemia or GERD. Conclusions: These findings may suggest a complex and context-dependent relationship between PPI use and lung cancer outcomes, emphasizing the need for individualized risk assessments and careful prescribing practices.