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The effectiveness of lipid-lowering drugs in combating cutaneous melanoma (CM) is a subject of ongoing debate in both in vitro and clinical studies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>This study aims to evaluate the causal relationship between various lipid-lowering drug targets, namely 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, targeted by statins), Proprotein convertase subtilisin\/kexin type 9 (PCSK9, targeted by alirocumab and evolocumab), and Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and the outcomes of cutaneous melanoma. To mimic the effects of lipid-lowering drugs, we utilized two genetic tools: analysis of polymorphisms affecting the expression levels of drug target genes, and genetic variations linked to low-density lipoprotein cholesterol levels and drug target genes. These variations were sourced from genome-wide association studies (GWAS). We applied Summary-data-based Mendelian Randomization (SMR) and Inverse Variance Weighted Mendelian Randomization (IVW-MR) to gauge the effectiveness of these drugs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our findings, with SMR results showing an odds ratio (OR) of 1.44 (95% CI: 1.08\u20131.92; <jats:italic>P<\/jats:italic>\u2009=\u20090.011) and IVW-MR results indicating an OR of 1.56 (95% CI: 1.10\u20132.23; <jats:italic>P<\/jats:italic>\u2009=\u20090.013), demonstrate a positive correlation between PCSK9 expression and increased risk of CM. However, no such correlations were observed in other analyses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The study concludes that PCSK9 plays a significant role in the development of CM, and its inhibition is linked to a reduced risk of the disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-024-12366-8","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:02:08Z","timestamp":1715947328000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association of lipid-lowering drug targets with risk of cutaneous melanoma: a mendelian randomization study"],"prefix":"10.1186","volume":"24","author":[{"given":"Lusheng","family":"Miao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taosheng","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"issue":"12","key":"12366_CR1","doi-asserted-by":"publisher","first-page":"5844","DOI":"10.1016\/j.asjsur.2023.08.167","volume":"46","author":"L Zhi","year":"2023","unstructured":"Zhi L, Xu X. 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