{Reference Type}: Journal Article
{Title}: Lipid-lowering medications and risk of malignant melanoma: a Mendelian randomization study.
{Author}: Yang B;Wang H;Song W;Feng J;Hou S;
{Journal}: Front Oncol
{Volume}: 14
{Issue}: 0
{Year}: 2024
{Factor}: 5.738
{DOI}: 10.3389/fonc.2024.1408972
{Abstract}: UNASSIGNED: The relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis.
UNASSIGNED: Genetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran's Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk.
UNASSIGNED: IVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439-0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026-1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma.
UNASSIGNED: HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.