Examining the Causal Connection between Lipid-lowering Medications and Malignant Meningiomas through Drug-target Mendelian Randomization Analysis

Abstract

Objectives: This study aims to investigate the causal link between the use of statins, a type of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and the risk of developing malignant meningiomas, which are aggressive and recurrent tumors of the central nervous system with limited treatment options. Methods: Using Mendelian Randomization (MR) analysis, the study explored the relationship between genetic variants related to the expression of lipid-lowering drug targets (HMGCR, PCSK9, NPC1L1, and APOB) and malignant meningiomas. The analysis utilized data from Genome-Wide Association Studies (GWAS) and expression quantitative trait loci (eQTL) databases, with a focus on the genetic homogeneity of the Finnish population. Instrumental variables for the MR analysis were derived from significant eQTLs for the mentioned drug targets. Results: The MR analysis found a significant association between genetic variants linked to HMGCR inhibitor (statin) exposure and a reduced risk of malignant meningiomas. Specifically, an increased expression of the HMGCR gene in the blood was associated with lower susceptibility to malignant meningiomas (Odds Ratio [OR] = 2.57, 95% Confidence Interval [CI] = 1.05 - 6.31; p = 0.039). No significant associations were observed for other lipid-lowering drug targets. Conclusion: Preliminary evidence suggests that statin use may lower the risk of developing malignant meningiomas, indicating a potential therapeutic benefit for managing this type of cancer. However, further research, including clinical trials, is necessary to confirm these findings and understand the mechanisms behind the protective effect of statins against malignant meningiomas.