{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T23:28:22Z","timestamp":1780356502067,"version":"3.54.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although previous studies have indicated an association between low-density lipoprotein (LDL) and skin diseases, their causal effects remain inconclusive. This study aimed to assess the causal relationship between genetically proxied lipid-lowering drugs and skin cancers and psoriasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two-sample Mendelian randomization (MR) analysis was performed using single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was used to determine causal relationships. The \u201cleave-one-out\u201d sensitivity test, Cochran\u2019s Q-statistic and MR-Egger intercept were used to assess heterogeneity and horizontal pleiotropy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase subtilisin-kexin type 9 (PCSK9) as genetically proxied lipid-lowering drugs. Genetically proxied inhibition of HMGCR (stains) was causally associated with reduced risk of nonmelanoma skin cancer (OR 0.982, 95% CI 0.967\u20130.997, <jats:italic>p<\/jats:italic>\u2009=\u20090.016 by weighted median; OR 0.977, 95% CI 0.966\u20130.989, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001 by IVW) and psoriasis (OR 0.585, 95% CI 0.378\u20130.905, <jats:italic>p<\/jats:italic>\u2009=\u20090.016 by IVW), while PCSK9 inhibition (alirocumab) was causally associated with reduced risk of psoriasis (OR 0.560, 95% CI 0.413\u20130.761 by weighted median; OR 0.564, 95% CI 0.447\u20130.712 by IVW; <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) in the ieu-b-5089 dataset. Similar results were observed in the ieu-b-110 dataset for HMGCR and PCSK9. Sensitivity analysis revealed no evidence of heterogeneity or horizontal pleiotropy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study revealed the existing HMGCR inhibitors (stains) might be protective for reducing nonmelanoma skin cancer risk, and HMGCR inhibitors (stains) and PCSK9 inhibitor (alirocumab) might be promising for reducing psoriasis risk in the European population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1396036","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T12:42:01Z","timestamp":1727268121000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Causal effects of lipid-lowering drugs on skin diseases: a two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"11","author":[{"given":"Yong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Queqiao","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1001\/jamadermatol.2016.5538","article-title":"Global skin disease morbidity and mortality: an update from the global burden of disease study 2013","volume":"153","author":"Karimkhani","year":"2017","journal-title":"JAMA Dermatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.jaad.2021.03.109","article-title":"United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019","volume":"85","author":"Aggarwal","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"959289","DOI":"10.3389\/fmed.2022.959289","article-title":"Classic and new strategies for the treatment of advanced melanoma and non-melanoma skin cancer","volume":"9","author":"Rubatto","year":"2023","journal-title":"Front Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.jaad.2020.11.047","article-title":"Five-year survival in patients with nodular and superficial spreading melanomas in the US population","volume":"84","author":"Allais","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5225","DOI":"10.1158\/1078-0432.CCR-21-0809","article-title":"5-year outcomes with Cobimetinib plus Vemurafenib inBRAFV600 mutation\u2013positive advanced melanoma: extended follow-up of the coBRIM study","volume":"27","author":"Ascierto","year":"2021","journal-title":"Clin Cancer Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e005082","DOI":"10.1136\/jitc-2022-005082","article-title":"Update in the treatment of non-melanoma skin cancers: the use of PD-1 inhibitors in basal cell carcinoma and cutaneous squamous-cell carcinoma","volume":"10","author":"Ascierto","year":"2022","journal-title":"J Immunother Cancer"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/jdv.13854","article-title":"A systematic review of worldwide epidemiology of psoriasis","volume":"31","author":"Michalek","year":"2017","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.3390\/life11101109","article-title":"Psoriasis therapy and skin cancer: a review","volume":"11","author":"Butr\u00f3n-Bris","year":"2021","journal-title":"Lifestyles"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"adv00032","DOI":"10.2340\/00015555-3386","article-title":"Psoriasis and treatment: past, present and future aspects","volume":"100","author":"Reid","year":"2020","journal-title":"Acta Derm Venereol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/ph17010014","article-title":"Risk of melanoma and non-melanoma skin Cancer in patients with psoriasis and psoriatic arthritis treated with targeted therapies: a systematic review and meta-analysis","volume":"17","author":"Krzysztofik","year":"2024","journal-title":"Pharmaceuticals"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. 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