دورية أكاديمية
أعرض في EDS

Association of lipid-lowering drug targets with risk of cutaneous melanoma: a mendelian randomization study.

التفاصيل البيبلوغرافية
العنوان: Association of lipid-lowering drug targets with risk of cutaneous melanoma: a mendelian randomization study.
المؤلفون: Miao L; Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Miao T; Guangzhou University of Chinese Medicine, Guangzhou, China., Zhang Y; Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Hao J; Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. haojin_cq@163.com.
المصدر: BMC cancer [BMC Cancer] 2024 May 17; Vol. 24 (1), pp. 602. Date of Electronic Publication: 2024 May 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2001-
مواضيع طبية MeSH: Melanoma*/genetics , Melanoma*/drug therapy , Mendelian Randomization Analysis* , Skin Neoplasms*/genetics , Skin Neoplasms*/drug therapy , Proprotein Convertase 9*/genetics , Hydroxymethylglutaryl CoA Reductases*/genetics , Genome-Wide Association Study*, Humans ; Melanoma, Cutaneous Malignant ; Antibodies, Monoclonal, Humanized/therapeutic use ; Polymorphism, Single Nucleotide ; Membrane Transport Proteins/genetics ; Membrane Proteins/genetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Ezetimibe/therapeutic use ; Hypolipidemic Agents/therapeutic use ; Hypolipidemic Agents/pharmacology
مستخلص: Background: Melanoma proliferation is partly attributed to dysregulated lipid metabolism. The effectiveness of lipid-lowering drugs in combating cutaneous melanoma (CM) is a subject of ongoing debate in both in vitro and clinical studies.
Method: 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.
Results: Our findings, with SMR results showing an odds ratio (OR) of 1.44 (95% CI: 1.08-1.92; P = 0.011) and IVW-MR results indicating an OR of 1.56 (95% CI: 1.10-2.23; P = 0.013), demonstrate a positive correlation between PCSK9 expression and increased risk of CM. However, no such correlations were observed in other analyses.
Conclusion: 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.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: Cutaneous melanoma; Lipid-lowering drugs; Mendelian randomization; Proprotein convertase subtilisin/Kexin type 9(PCSK9)
المشرفين على المادة: 0 (PCSK9 protein, human)
0 (HMGCR protein, human)
0 (NPC1L1 protein, human)
0 (alirocumab)
0 (evolocumab)
تواريخ الأحداث: Date Created: 20240517 Date Completed: 20240518 Latest Revision: 20240521
رمز التحديث: 20240521
مُعرف محوري في PubMed: PMC11102253
DOI: 10.1186/s12885-024-12366-8
PMID: 38760735
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2407
DOI:10.1186/s12885-024-12366-8