Associations of aspirin use with pancreatic cancer risk: a meta-analysis of cohort studies with exploratory population- and exposure-stratified analyses

Considering various confounding factors, the preventive effect of aspirin on pancreatic cancer remains controversial. This study aimed to evaluate the association between aspirin use and the risk of pancreatic cancer in different populations and explore possible influencing factors. A comprehensive search was performed in PubMed, Web of Science, Embase, and Cochrane Library from database inception to 31 March 2025. The primary outcome was pancreatic cancer incidence, assessed using adjusted hazard ratios with 95% confidence intervals (CIs) and prediction intervals. This study was registered in PROSPERO (CRD420251002604). Six cohort studies were included. Pooled analysis showed aspirin use was associated with reduced pancreatic cancer risk (hazard ratio = 0.80, 95% CI: 0.72-0.88, 95% prediction interval: 0.65-0.97, P < 0.001). High heterogeneity ( I ² = 69.9%, τ ² = 0.008) resulted in low Grading of Recommendations, Assessment, Development and Evaluation (evidence‑based grading system for evidence strength). Exploratory subgroup analyses suggested lower risk in diabetes patients (hazard ratio = 0.59, 95% CI: 0.52-0.68, P < 0.001), BMI less than 25 kg/m² (hazard ratio = 0.52, 95% CI: 0.43-0.64, P < 0.001), and nondrinkers (hazard ratio = 0.58, 95% CI: 0.51-0.65, P < 0.001). No significant association was found in women (hazard ratio = 0.74, 95% CI: 0.55-1.00, P = 0.102) or high ‑ dose aspirin users (hazard ratio = 0.82, 95% CI: 0.67-1.00, P = 0.102). Aspirin may be associated with a lower pancreatic cancer risk, but there is considerable heterogeneity. Diabetes, BMI and alcohol consumption may be potential influencing factors and sources of heterogeneity.