Lipid-lowering medications and risk of malignant melanoma: a Mendelian randomization study.
Front Oncol
; 14: 1408972, 2024.
Article
em En
| MEDLINE
| ID: mdl-38974243
ABSTRACT
Background:
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.Methods:
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.Results:
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.Conclusions:
HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.
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MEDLINE
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En
Ano de publicação:
2024
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Article