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ENGLISH ABSTRACT
2型糖尿病与甲状腺乳头状癌关系的两样本孟德尔随机化研究
王嘉文
林秋玉
姜楠
赵爽言
王宇鑫
郭莹
林承赫
作者及单位信息
·
DOI： 10.3760/cma.j.cn321828-20240528-00180
A two-sample Mendelian randomization study of the association between type 2 diabetes mellitus and papillary thyroid cancer
Wang Jiawen
Lin Qiuyu
Jiang Nan
Zhao Shuangyan
Wang Yuxin
Guo Ying
Lin Chenghe
Authors Info & Affiliations
Wang Jiawen
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
Lin Qiuyu
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
Jiang Nan
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
Zhao Shuangyan
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
Wang Yuxin
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
Guo Ying
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
Lin Chenghe
Department of Nuclear Medicine, the First Hospital of Jilin University, Changchun 130021, China
·
DOI： 10.3760/cma.j.cn321828-20240528-00180
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摘要

目的采用孟德尔随机化(MR)研究探讨2型糖尿病(T2DM)、1型糖尿病(T1DM)、体质指数(BMI)与甲状腺乳头状癌之间的因果关系。

方法以公开发表的全基因组关联研究(GWAS)作为数据源，筛选出与暴露相关的单核苷酸多态性(SNPs)作为工具变量，采用两样本MR法中的逆方差加权(IVW)、加权中位数、MR-Egger、简单模式和加权模式法评估T2DM、T1DM、BMI与甲状腺乳头状癌之间的因果关联。通过异质性分析、多效性分析及敏感性分析评估结果的可靠性和稳定性。

结果针对T2DM、T1DM、BMI，最终分别筛选出118、76、486个强工具变量进行两样本MR分析。在5种MR分析方法中，IVW分析的T2DM与甲状腺乳头状癌因果关系的结果有统计学意义[比值比( OR)＝1.147(95% CI：1.026～1.282)， P＝0.016]，其余4种分析方法的遗传效应值 β与IVW的 β方向相同；异质性分析、多效性分析及敏感性分析结果均显示 P>0.05。T1DM[IVW法： OR＝1.000(95% CI：0.952～1.051)， P＝0.994]与甲状腺乳头状癌、BMI[IVW法： OR＝1.214(95% CI：0.923～1.598)， P＝0.166]与甲状腺乳头状癌均无明确的因果关系。

结论T2DM与甲状腺乳头状癌之间存在因果关联，即T2DM会增加甲状腺乳头状癌发生的风险。T1DM、BMI与甲状腺乳头状癌均无明确的因果关系。

糖尿病，2型;甲状腺肿瘤;癌，乳头状;孟德尔随机化分析
ABSTRACT

ObjectiveTo investigate the causal relationship between type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), body mass index (BMI) and papillary thyroid cancer using Mendelian randomization(MR) study.

MethodsPublicly available genome-wide association studies (GWAS) were used as the data source to screen single nucleotide polymorphisms significantly associated with exposure factors (instrumental variables), and the inverse variance weighting (IVW), weighted median, MR-Egger analysis, simple mode, and weighted mode of two-sample MR were used to assess the causal association between T2DM, T1DM, BMI and papillary thyroid cancer. The reliability and stability of the results were assessed by heterogeneity analysis, multiple validity analysis and sensitivity analysis.

ResultsA total of 118 strong instrumental variables for T2DM, 76 for T1DM, and 486 for BMI were screened respectively to conduct two-sample MR analysis. Among the 5 MR analysis methods, the results of the IVW method showed that T2DM was significantly associated with papillary thyroid cancer (odds ratio ( OR)=1.147, 95% CI: 1.026-1.282; P=0.016), and the genetic effect values ( β values) of the other 4 analysis methods and IVW method were in the same direction; the results of heterogeneity analysis, multiplicity analysis and sensitivity analysis showed all P>0.05. T1DM (IVW method: OR=1.000, 95% CI: 0.952-1.051; P=0.994) and papillary thyroid cancer, BMI (IVW method: OR=1.214, 95% CI: 0.923-1.598; P=0.166) and papillary thyroid cancer were not clearly causally related.

ConclusionsThere is a causal association between T2DM and papillary thyroid cancer, and T2DM increases the risk of papillary thyroid cancer. There is no clear causal association between T1DM, BMI and papillary thyroid cancer.

Diabetes mellitus, type 2;Thyroid neoplasms;Carcinoma, papillary;Mendelian randomization analysis
Lin Chenghe, Email: mocdef.3ab617691hhcnil
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引用本文

王嘉文,林秋玉,姜楠,等. 2型糖尿病与甲状腺乳头状癌关系的两样本孟德尔随机化研究[J]. 中华核医学与分子影像杂志,2025,45(03)：164-168.

DOI:10.3760/cma.j.cn321828-20240528-00180

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甲状腺癌是内分泌系统中最常见的恶性肿瘤 [ 1 , 2 ]，其发病率占所有恶性肿瘤的1%～5.3% [ 3 ]。我国甲状腺癌患病率逐年增加，且发病年龄逐渐年轻化，其中甲状腺乳头状癌(papillary thyroid cancer, PTC)发病率最高，占总体甲状腺癌中的96% [ 4 ]。2型糖尿病(type 2 diabetes mellitus, T2DM)是我国糖尿病患者的主要类型，是胰岛素抵抗或胰岛功能减退等引发的一系列代谢紊乱综合征。既往研究表明，T2DM与甲状腺癌发病有关 [ 5 ]。一项包含20个队列研究的荟萃分析显示，任何类型的糖尿病患者患甲状腺癌的风险都会升高 [ 1 ]。同时，多项研究表明体质指数(body mass index, BMI)的增高会增加甲状腺癌的发病率 [ 6 , 7 ]，BMI也是T2DM的危险因素 [ 8 ]。传统的流行病学研究不能很好地确定甲状腺癌的真正危险因素，因此，本研究采用孟德尔随机化(Mendelian randomization, MR)方法探讨T2DM、1型糖尿病(type 1 diabetes mellitus, T1DM)、BMI与PTC发生风险的潜在关联性，旨在为揭示糖尿病、BMI与甲状腺癌的关联提供科学依据，并为甲状腺癌的预防和治疗提供新的方向。
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备注信息
A
林承赫，Email: mocdef.3ab617691hhcnil
B

王嘉文：研究实施，数据处理、论文撰写；林秋玉：研究指导、论文修改；姜楠、赵爽言、王宇鑫、郭莹：数据分析、图形建立；林承赫：研究指导、论文审阅

C
所有作者声明无利益冲突
D
国家自然科学基金 (81901774)
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