Su_2025_Sci.Rep_15_3282

Previous studies have found that dyslipidemia is a risk factor for pancreatic cancer (PC), and that lipid-lowering drugs may reduce the risk of PC. However, it is not clear whether dyslipidemia causes PC. The Mendelian randomization (MR) study aimed to investigate the causal role of lipid traits in pancreatic cancer and to assess the potential impact of lipid-lowering drug targets on pancreatic cancer. Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for PC were obtained from an independent GWAS datasets. Colocalization analyses were performed to validate the robustness of the results. No significant effect of lipid-lowering drug targets on PC risk was found. Genetic mimicry of lipoprotein lipase (LPL) was potentially associated with PC risks. Significant MR associations were observed in the discovery dataset (OR 1.64 [95% CI 1.24-2.16], p = 4.48*10(-4)) with PC in one dataset. However, the finding was not verified in the replication dataset. Our findings do not support dyslipidemia as a causal factor for PC. Among lipid-lowering drug targets, LPL is the potential drug target in PC.