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Updated: Jun 27, 2026
Experimental Metastasis Assay
Published on: August 24, 2010
Lipids, lipid-lowering drug target genes and pancreatic cancer: a Mendelian randomization study
Yuxuan Zhan1, Kai Zhang1, Yiqun Fan2
1School of Public Health and Institute of Wenzhou and Liangzhu Laboratory, Zhejiang University, Hangzhou, 310058, China.
Background:
Pancreatic cancer (PC) is a malignant tumor with a low survival rate. Lipid modifiers show potential for PC therapy, but evidence is lacking.
Aim:
This Mendelian randomization (MR) study aimed to explore the relationship between lipid traits, and lipid-lowering drug target genes with PC risk.
Method:
Genetic instrumental variables associated with lipid traits and lipid-lowering drug target genes were used to perform MR analyses of PC risk. MR estimation was based on genome-wide association study data from two large sample sets, and the MR results were meta-analyzed to assess their impact on PC risk. To ensure the reliability of lipid-modifying drug targets, we conducted a Summary Data-based Mendelian Randomization (SMR) analysis. Additionally, a two-step MR analysis was employed to explore potential mediating effects.
Results:
In two independent datasets, HMG-CoA reductase (HMGCR) inhibition was statistically associated with a lower risk of PC (OR 0.50, [95% CI 0.25-1.00]; p = 0.0453). The results were further supported by SMR analysis, which showed a similar association (OR 0.51, [95% CI 0.28-0.96]; p = 0.0369). Mediation analysis revealed that 11.69% of the protective effect of HMGCR inhibitors on PC is mediated through lower BMI levels. No significant effect of lipid traits and the other eight lipid-lowering drug targets on PC risk was found.
Conclusion:
This study suggests that HMGCR may be a potential drug target for the treatment or prevention of PC, providing important insights into the use of lipid-targeted drugs in PC therapy.
