Abstract：
Our study aimed to investigate the role of lipids in melanoma risk and the effect of lipid-lowering drug targets on melanoma. Using Mendelian Randomization analysis, we examined the genetic agents of nine lipid-lowering drugs and their association with melanoma risk. We found that genetically proxied inhibition of HMGCR, ABCG5/ABCG8, and ANGPTL3 was associated with a reduced risk of melanoma. On the other hand, inhibition of LPL and Apo-B100 was significantly associated with an increased risk of melanoma. Sensitivity analyses did not reveal any statistical evidence of bias from pleiotropy or genetic confounding. We did not find a robust association between lipid traits NPC1L1, PCSK9, APOC3 inhibition, and melanoma risk. These findings were validated using two independent lipid datasets. Our analysis also revealed that HMGCR, ANGPTL3, and ABCG5/ABCG8 inhibitors reduced melanoma risk independent of their effects on lipids. This suggests that these targets may have potential for melanoma prevention or treatment. In conclusion, our study provides evidence for a causal role of lipids in melanoma risk and highlights specific lipid-lowering drug targets that may be effective in reducing the risk of melanoma. These findings contribute to the understanding of the underlying mechanisms of melanoma development and provide potential avenues for further research and therapeutic interventions.
摘要：
我们的研究旨在研究脂质在黑色素瘤风险中的作用以及降脂药物靶标对黑色素瘤的影响。使用孟德尔随机化分析，我们研究了9种降脂药的遗传因素及其与黑色素瘤风险的关系.我们发现HMGCR的遗传代理抑制，ABCG5/ABCG8和ANGPTL3与黑色素瘤风险降低相关。另一方面,LPL和Apo-B100的抑制与黑色素瘤风险增加显著相关.敏感性分析未发现任何统计学证据表明多效性或遗传混杂。我们没有发现脂质性状NPC1L1，PCSK9，APOC3抑制，和黑色素瘤的风险。使用两个独立的脂质数据集来验证这些发现。我们的分析还显示，HMGCR，ANGPTL3和ABCG5/ABCG8抑制剂独立于其对脂质的影响降低了黑色素瘤的风险。这表明这些靶标可能具有预防或治疗黑素瘤的潜力。总之,我们的研究提供了脂质在黑色素瘤风险中的因果作用的证据,并强调了可能有效降低黑色素瘤风险的特定降脂药物靶点.这些发现有助于理解黑色素瘤发展的潜在机制，并为进一步的研究和治疗干预提供了潜在的途径。
