Zhang Qihong, Lan Xiabin
Department of Anorectal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
Department of Thyroid Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Medicine (Baltimore). 2025 Feb 28;104(9):e41633. doi: 10.1097/MD.0000000000041633.
Currently, the precise interplay between autoimmune thyroiditis, particularly Hashimoto thyroiditis, and thyroid cancer remains ambiguous. While certain observational studies suggest autoimmune thyroiditis (including Hashimoto thyroiditis) as a predisposing factor for thyroid cancer. Nevertheless, it is still uncertain whether autoimmune thyroiditis is independently associated with thyroid cancer. We employed Mendelian randomization (MR) study methodology, a genetic analysis approach, to evaluate the causal impact of autoimmune thyroiditis on the occurrence of thyroid cancer. We obtained and synthesized statistical data by utilizing public available genome-wide association studies (GWAS). Our study utilized GWAS summary statistics datasets associated with autoimmune thyroiditis (including Hashimoto thyroiditis) as the exposure data source and selected GWAS summary statistics datasets related to thyroid cancer as the outcome data source. Single nucleotide polymorphisms closely associated with autoimmune thyroiditis were chosen as instrumental variables. We conducted 2-sample MR analyses to elucidate the causal association between autoimmune thyroiditis and thyroid cancer. The inverse variance-weighted (IVW) method was employed as the primary methodology, supplemented by additional MR methods including MR-Egger regression, weighted median, simple mode, and weighted mode analyses, to bolster the robustness of our findings. The MR analysis conducted using the IVW method did not confirm a causal relationship between autoimmune thyroiditis and thyroid cancer (odds ratio [OR] = 0.8554, 95% confidence interval [CI]: 0.7193 to 1.0172, P = .0772; OR = 0.8477, 95% CI: 0.7159 to 1.0039, P = .0555; and OR = 1.1324, 95% CI: 0.9342 to 1.3725, P = .2052, from 3 eligible dataset analyses, respectively). Additionally, MR analysis did not observe a causal association between Hashimoto thyroiditis and thyroid cancer (OR = 1.0449, 95% CI: 0.9400 to 1.1615, P = .4155; and OR = 0.9897, 95% CI: 0.8174 to 1.1984, P = .9159, from 2 eligible dataset analyses, respectively). Consistency in results across alternative MR methods was observed. This study employing MR methodology indicates the absence of significant causal relationship between exposure to autoimmune thyroiditis (including Hashimoto thyroiditis) and thyroid cancer. Further validation through larger-scale studies with increased sample sizes is warranted in future investigations.
目前，自身免疫性甲状腺炎，尤其是桥本甲状腺炎与甲状腺癌之间的确切相互作用仍不明确。虽然某些观察性研究表明自身免疫性甲状腺炎（包括桥本甲状腺炎）是甲状腺癌的一个诱发因素。然而，自身免疫性甲状腺炎是否与甲状腺癌独立相关仍不确定。我们采用孟德尔随机化（MR）研究方法，一种基因分析方法，来评估自身免疫性甲状腺炎对甲状腺癌发生的因果影响。我们通过利用公开可用的全基因组关联研究（GWAS）来获取和综合统计数据。我们的研究使用与自身免疫性甲状腺炎（包括桥本甲状腺炎）相关的GWAS汇总统计数据集作为暴露数据源，并选择与甲状腺癌相关的GWAS汇总统计数据集作为结果数据源。选择与自身免疫性甲状腺炎密切相关的单核苷酸多态性作为工具变量。我们进行了两样本MR分析，以阐明自身免疫性甲状腺炎与甲状腺癌之间的因果关联。采用逆方差加权（IVW）方法作为主要方法，并辅以其他MR方法，包括MR-Egger回归、加权中位数、简单模式和加权模式分析，以增强我们研究结果的稳健性。使用IVW方法进行的MR分析未证实自身免疫性甲状腺炎与甲状腺癌之间存在因果关系（优势比[OR]=0.8554，95%置信区间[CI]：0.7193至1.0172，P=0.0772；OR=0.8477，95%CI：0.7159至1.0039，P=0.0555；以及OR=1.1324，95%CI：0.9342至1.3725，P=0.2052，分别来自3个符合条件的数据集分析）。此外，MR分析未观察到桥本甲状腺炎与甲状腺癌之间存在因果关联（OR=1.0449，95%CI：0.9400至1.1615，P=0.4155；以及OR=0.9897，95%CI：0.8174至1.1984，P=0.9159，分别来自2个符合条件的数据集分析）。观察到不同MR方法的结果具有一致性。这项采用MR方法的研究表明，暴露于自身免疫性甲状腺炎（包括桥本甲状腺炎）与甲状腺癌之间不存在显著的因果关系。未来的研究有必要通过更大规模、样本量增加的研究进行进一步验证。
