甲状腺功能与甲状腺癌的因果关系:双样本孟德尔随机化分析OA

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-vari-ance weighted method,supplemented by four additional analytical approaches:the weighted median estimator,MR-Egger re-gression,the simple mode,and the weighted mode.In addition,horizontal pleiotropy was assessed using the MR-Egger in-tercept 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 a-nalysis was also conducted.Results:The MR analysis showed that elevated levels of thyroid peroxidase(TPO)were associ-ated 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-PRES-SO global test(P=0.973)indicated evidence of horizontal pleiotropy.No significant heterogeneity was detected by Coch-ran'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-cy-tokine receptor interaction signaling pathways.Conclusion:High levels of TPO may reduce the risk of FTC.