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评估代谢综合征对甲状腺癌的影响:孟德尔随机化方法的见解

Assessing the influence of metabolic syndrome on thyroid cancer: insights from a Mendelian randomization approach.

作者信息

Ru Xiaosong, Su Ziying, Guo Yong

机构信息

The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Discov Oncol. 2025 Jun 10;16(1):1048. doi: 10.1007/s12672-025-02760-4.

Abstract

BACKGROUND

The results of observational studies on the causal relationship between metabolic syndrome (MetS) and thyroid cancer (TC) are controversial. This study aimed to explore the potential causal link between metabolic syndrome (MetS) and thyroid cancer (TC) by Mendelian randomization (MR) analysis. Additionally, the genetic correlation was evaluated using Linkage Disequilibrium Score Regression (LDSC).

METHODS

In this study, we derived instrumental variables (IVs) linked to metabolic syndrome and its components from publicly accessible genome-wide association study (GWAS) databases. These IVs were then used in a MR with TC data from the Finnish population. The primary method of analysis was inverse variance weighted (IVW), supplemented by various sensitivity analyses to ensure the robustness and reliability of the findings.

RESULTS

MR analysis identified a significant positive causal link between MetS and TC (OR = 1.7003, 95%CI = 1.2631-2.2888, P = 0.0005), while high-density lipoprotein cholesterol (HDL-C) exhibited a negative causal relationship (OR = 0.7868,95%CI = 0.6822-0.9076, P = 0.0010). Sensitivity tests showed no evidence of heterogeneity or horizontal pleiotropy. LDSC analyses did not detect significant genetic correlations between MetS and its components and TC.

CONCLUSIONS

Our results indicate that MetS substantially elevates the risk of TC, while HDL-C may have a protective effect against TC. These findings offer fresh perspectives on the potential causal link between MetS and TC.

摘要

背景

关于代谢综合征(MetS)与甲状腺癌(TC)因果关系的观察性研究结果存在争议。本研究旨在通过孟德尔随机化(MR)分析探讨代谢综合征(MetS)与甲状腺癌(TC)之间潜在的因果联系。此外,使用连锁不平衡评分回归(LDSC)评估遗传相关性。

方法

在本研究中,我们从公开可用的全基因组关联研究(GWAS)数据库中导出与代谢综合征及其组分相关的工具变量(IVs)。然后将这些IVs用于对来自芬兰人群的TC数据进行MR分析。主要分析方法是逆方差加权(IVW),并辅以各种敏感性分析以确保研究结果的稳健性和可靠性。

结果

MR分析确定MetS与TC之间存在显著的正因果关系(OR = 1.7003,95%CI = 1.2631 - 2.2888,P = 0.0005),而高密度脂蛋白胆固醇(HDL-C)呈现负因果关系(OR = 0.7868,95%CI = 0.6822 - 0.9076,P = 0.0010)。敏感性检验未发现异质性或水平多效性的证据。LDSC分析未检测到MetS及其组分与TC之间存在显著的遗传相关性。

结论

我们的结果表明,MetS会大幅增加TC风险,而HDL-C可能对TC具有保护作用。这些发现为MetS与TC之间潜在的因果联系提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8b6/12151941/0070196d7cab/12672_2025_2760_Fig1_HTML.jpg

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