PCSK9抑制剂的应用与消化道肿瘤之间的因果关系:一项药物靶向孟德尔随机化研究
Investigating the causal relationship between PCSK9 inhibitors and digestive tract tumors:a mendelian randomization study
虞燕波 1支德源1
作者信息
- 1. 首都医科大学附属北京友谊医院全科医学科 北京 100050
- 折叠
摘要
目的 使用药物靶向孟德尔随机化的方法探索前蛋白转换酶枯草溶菌素9(PCSK9)抑制剂的应用与消化道肿瘤发生风险的因果关系.方法 应用药物靶向孟德尔随机化分析,探讨PCSK9抑制剂的应用对消化道肿瘤(包括食管癌、胃癌和结直肠癌)发病率的因果关系.进行两样本孟德尔随机化研究,评估脂质[包括低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白(Apo)A-1和ApoB]与消化道肿瘤发病率之间的潜在关系,并以此判断PCSK9抑制剂抑癌作用的途径.结果 通过药物靶向孟德尔随机化的方法,结果发现PCSK9抑制剂的应用与胃癌风险的下降显著相关(OR=0.36,95％CI:0.18～0.72,P=0.004),未发现PCSK9抑制剂与其他类型癌症之间存在显著的因果关系.单因素两样本孟德尔随机化分析未发现脂质成分的变化与胃癌发生率之间存在显著因果关系的关联,而多因素孟德尔随机化分析表明ApoB的水平下降与胃癌发生率的升高存在弱的因果关系关联(P=0.03,β=0.17,95％CI:0.01～0.32).结论 PCSK9抑制剂的应用有助于降低患者罹患胃癌的风险.然而,这种保护作用独立于PCSK9抑制剂的降脂作用,单纯的血脂下降无法降低胃癌的发生风险.本研究观测到的抑癌作用可能归因于PCSK9抑制剂除降脂作用外的其他机制.
Abstract
[Abstrac]Objective To explore the causal relationship between proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitor and the risk of digestive tract tumors using Mendelian randomization analyses.Methods The drug-target Mendelian randomization analyses was used to explore the impact of PCSK9 inhibitors on digestive tract tumors,encompassing esophageal cancer,gastric cancer,and colorectal cancer.Two-sample Mendelian randomization analyses were conducted to assess the potential relationships between lipids[low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),apolipoprotein(Apo)A-1 and ApoB)]and the risk of digestive tract tumors.The aim of these analyses was to determine if the effects of PCSK9 inhibitors on digestive tract tumors are mediated through their lipid-lowering ac-tions.Results The usage of PCSK9 inhibitors was statistically significantly associated with a decreased risk of gastric cancer(OR=0.36,95％CI:0.18-0.72,P=0.004).No statistically significant causal relationships were observed between PCSK9 inhibitors and other types of cancers.Univariable analysis revealed no statistically significant associations between variations in the four lipids and the incidence of gastric canc-er.Nevertheless,the multivariable Mendelian randomization analysis(using LASSO)indicated a potential causal relationship between changes in ApoB and gastric cancer(P=0.03,β=0.17,95％CI:0.01-0.32).Conclusion This study provides evidence for a protective effect of PCSK9 inhibition on gastric cancer risk.However,this protective effect appears to be independent of its lipid-lowering actions.The observed re-duction in gastric cancer risk may be attributed to other mechanisms or pathways related to PCSK9 inhibition.
关键词
胃肿瘤/PCSK9抑制剂/消化道肿瘤/因果关系/孟德尔随机化Key words
Stomach neoplasms/PCSK9 inhibitors/Digestive tract neoplasms/Causality/Mendelian randomization引用本文复制引用
出版年
2024
NETL
NSTL
万方数据