摘要
目的:本研究旨在通过孟德尔随机化(mendelian randomization,MR)方法,探讨5种甲状腺功能指标与甲状腺癌之间是否存在因果关系。方法:从IEU Open GWAS数据库获取甲状腺功能汇总数据,从IEU Open GWAS数据库及芬兰数据库提取甲状腺癌GWAS数据。采用逆方差加权法,同时使用其他4种分析方法进行补充(包括加权中位数法、MR-Egger回归、简单众数法、加权众数法),进行双样本MR分析。此外,采用MR-Egger截距和MR-PRESSO方法进行基因多效性检测,Cochran Q检验及留一法评估结果的异质性和敏感性,并进行反向MR分析。结果:MR分析结果显示,甲状腺过氧化物酶(thyroid peroxidase,TPO)水平升高与滤泡状甲状腺癌(follicular thyroid cancer,FTC)发生风险呈负相关(OR=0.504,95%CI:0.299~0.848,P=0.010)。多效性检验(P=0.757)与MR-PRESSO全局检验(P=0.973)均未检测到明显的水平多效性。异质性检验表明不存在异质性(P=0.963)。反向MR分析结果显示,FTC与TPO之间没有显著相关性(P>0.05)。功能富集分析结果显示,TPO主要与细胞粘附、细胞因子-细胞因子受体相互作用等信号通路有关。结论:高水平TPO能够降低FTC的患病风险。
Objective:This study aims to investigate the causal relationship between five thyroid function parameters and thyroid cancer using mendelian randomization(MR).Methods:The GWAS summary statistics for thyroid function were ac quired from the IEU OpenGWAS database.Data for thyroid cancer were extracted from both the IEU OpenGWAS database and the FinnGen database.We performed a two-sample Mendelian randomization analysis primarily using the inverse-variance weighted method,supplemented by four additional analytical approaches:the weighted median estimator,MR-Egger regression,the simple mode,and the weighted mode.In addition,horizontal pleiotropy was assessed using the MR-Egger intercept test and the MR-PRESSO test.Heterogeneity and sensitivity of the results were evaluated by the Cochran’s Q test and leave-one-out analysis,respectively.A reverse MR analysis was also conducted.Results:The MR analysis showed that elevated levels of thyroid peroxidase(TPO)were associated with a lower risk of follicular thyroid cancer(FTC)(OR=0.504,95%CI:0.299~0.848,P=0.010).Neither the MR-Egger intercept test(P=0.757)nor the MR-PRESSO global test(P=0.973)indicated evidence of horizontal pleiotropy.No significant heterogeneity was detected by Cochran’s Q test(P=0.963).The reverse MR Analysis showed that there was no significant correlation between FTC and TPO(P>0.05).The functional enrichment analysis showed that TPO was primarily linked to the cell adhesion and cytokine-cytokine receptor interaction signaling pathways.Conclusion:High levels of TPO may reduce the risk of FTC.
作者
杨甜
李钰博
吴昊
刘铭
朱剑军
Yang Tian;Li Yubo;Wu Hao;Liu Ming;Zhu Jianjun(Department of Cell Biology and Medical Genetics,School of Basic Medical Science,Shanxi Medical University,Taiyuan O30001,Shanxi,China)
出处
《肿瘤预防与治疗》
2026年第1期21-27,共7页
Journal of Cancer Control And Treatment
基金
山西省应用基础研究项目(编号:2023021211114)
山西省高等教育“百亿工程”科技引导专项(编号:BYJL047)。
关键词
甲状腺功能
甲状腺过氧化物酶
甲状腺癌
孟德尔随机化
因果关系
Thyroid function
Thyroid peroxidase(TPO)
Thyroid cancer
Mendelian randomization
Causal relationship
