降脂药物和恶性黑色素瘤的风险:一个门德尔的随机化研究
BoWen Yang1,2, HanYu Wang3, WenYuan Song1,2
1Oncology, Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine, Dongguan, Guangdong, China.
Frontiers in oncology
|July 8, 2024
概括
降脂药物对黑色素瘤风险有不同的影响. 根据孟德尔随机分析,他类药物可能会增加风险,而PCSK9抑制剂可能会降低风险.
科学领域:
- 遗传学和癌症流行病学
- 药物基因组学 药物基因组学
- 心血管疾病治疗方法 治疗方法
背景情况:
- 脂质修饰药物与癌症风险,特别是黑色素瘤之间的关联是正在进行的研究领域,结果相互矛盾.
- 了解常见的降脂药物与黑色素瘤发病率之间的潜在因果关系对于临床实践至关重要.
研究的目的:
- 通过全面的门德尔随机化 (MR) 分析,调查常用的降脂药物和黑色素瘤发病率之间的潜在因果关系.
- 为了澄清有关脂质修饰药物对黑色素瘤结果的影响的有争议的发现.
主要方法:
- 进行了双样本的门德尔随机化分析,使用与LDL相关的药物标基因的遗传变异作为药物暴露的代理.
- 使用逆方差加权 (IVW),MR-Egger和加权中位数方法,并使用MR-PRESSO和性测试来解决水平性.
- 留下一个漏洞分析,科克兰的Q测试和漏洞图被用来评估MR发现的稳定性和可靠性.
主要成果:
- 对HMGCR (3-基-3-甲基氨酸-CoA减少酶) 基因表达的遗传代理与黑色素瘤风险降低有关 (OR:0.624,p=0.008).
- PCSK9 (proprotein convertase subtilisin/kexin type 9) 基因表达的遗传代理与黑色素瘤的风险增加有关 (OR: 1.233,p=0.025).
- 在NPC1L1 (Niemann-Pick C1-Like 1) 和黑色素瘤风险之间没有发现显著的关联.
结论:
- 通常称为他类药物的HMGCR抑制剂可能与黑色素瘤的风险增加有关.
- 像evolocumab和alirocumab这样的PCSK9抑制剂可能与黑色素瘤风险降低有关.
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