PDF(Pubmed)
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.
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.
摘要：
■血脂，调脂药物，癌症风险已经调查了一段时间。最近的研究表明，降脂药物可能会影响黑色素瘤的预后，尽管调查结果仍有争议。我们的研究旨在通过全面的孟德尔随机化（MR）分析来阐明常用降脂药与黑色素瘤发病率之间的潜在因果关系。
■LDL相关药物靶基因（来自全基因组关联研究的LDL-胆固醇）内的遗传变异可作为暴露于降脂药物的代理。我们使用方差逆加权(IVW)进行了双样本孟德尔随机化分析，MR-Egger,和加权中位数法。利用MR-PRESSO测试和多效性测试来识别和调整水平多效性。使用留一法评估孟德尔随机化结果的稳定性和可靠性，Cochran的Q测试,和漏斗图分析。使用赔率比（OR）来评估降脂药的遗传代理与黑色素瘤风险之间的因果关系。
■IVW分析显示HMGCR基因表达与黑色素瘤风险降低相关[OR:0.624(0.439-0.888);p=0.008]。相反，PCSK9基因表达与黑素瘤风险升高有关[OR:1.233(1.026-1.484);p=0.025]。在NPC1L1和黑色素瘤之间没有观察到显著的关联。
■HMGCR抑制剂（他汀类药物）可能会增加黑色素瘤的风险，而PCSK9抑制剂(evolocumab，alirocumab）可能会降低黑色素瘤风险。
■LDL相关药物靶基因（来自全基因组关联研究的LDL-胆固醇）内的遗传变异可作为暴露于降脂药物的代理。我们使用方差逆加权(IVW)进行了双样本孟德尔随机化分析，MR-Egger,和加权中位数法。利用MR-PRESSO测试和多效性测试来识别和调整水平多效性。使用留一法评估孟德尔随机化结果的稳定性和可靠性，Cochran的Q测试,和漏斗图分析。使用赔率比（OR）来评估降脂药的遗传代理与黑色素瘤风险之间的因果关系。
■IVW分析显示HMGCR基因表达与黑色素瘤风险降低相关[OR:0.624(0.439-0.888);p=0.008]。相反，PCSK9基因表达与黑素瘤风险升高有关[OR:1.233(1.026-1.484);p=0.025]。在NPC1L1和黑色素瘤之间没有观察到显著的关联。
■HMGCR抑制剂（他汀类药物）可能会增加黑色素瘤的风险，而PCSK9抑制剂(evolocumab，alirocumab）可能会降低黑色素瘤风险。
