PCSK9抑制剂与恶性瘤之间的因果关系:基于药物向的孟德尔随机化研究
Wenxin Wang1, Wei Li2, Dan Zhang1
1Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
Genes
|January 26, 2024
概括
亲蛋白转化酶子素/素9 (PCSK9) 抑制剂对癌症的发展具有双重影响. 它们与乳腺和肺癌的风险降低有关,但胃癌,肝癌和口腔癌的风险增加.
科学领域:
- 遗传学和流行病学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 蛋白转化酶亚素/素9 (PCSK9) 抑制剂是一种针对低密度脂蛋白胆固醇 (LDL-C) 的药物.
- 抑制PCSK9对瘤发育的潜在影响仍然是积极研究的领域.
- 门德尔随机化 (MR) 提供了一种强大的方法来推断使用遗传变异作为仪器变量的因果关系.
研究的目的:
- 调查PCSK9抑制与各种癌症的发展之间的潜在因果关系.
- 利用药物标的门德尔随机化方法来评估这些关系.
- 探索PCSK9抑制剂对不同类型癌症的保护性和增加风险的影响.
主要方法:
- 门德尔随机化 (MR) 分析使用与LDL-C水平相关的PCSK9基因位点附近的遗传变异.
- 冠心病 (CHD) 被用作积极对照来验证MR方法.
- 进行了反向MR和灵敏度分析,以解决潜在的偏差,如类型和反向因果关系.
主要成果:
- 在PCSK9抑制与乳腺癌 (OR 0.81-0.99) 和肺癌 (OR 0.65-0.94) 之间发现了显著的负因果关系.
- 相反,对于胃癌 (OR 1.14-1.75),肝癌 (OR 1.46-2.53),口腔和喉癌 (OR 4.49-6.33),以及宫内皮质瘤 (OR 4.56-7.12) 观察到一种积极的因果关系.
- 在膀,甲状腺,胰腺,结直肠,某些脏,大脑和食道癌症中没有发现显著的因果关系.
结论:
- PCSK9 抑制剂与癌症发展有着不同的因果关系.
- 这些药物可能会对乳腺癌和肺癌产生保护作用.
- 然而,它们似乎增加了胃癌,肝癌,口腔癌/喉癌以及宫内皮质瘤的风险.
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