甲状腺功能、自身免疫性甲状腺功能障碍与肺癌之间的因果关系：一项孟德尔随机化研究。
The causal relationship between thyroid function, autoimune thyroid dysfunction and lung cancer: a mendelian randomization study.
机构信息
Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
出版信息
BMC Pulm Med. 2023 Sep 11;23(1):338. doi: 10.1186/s12890-023-02588-0.
BACKGROUND
The role of thyroid hormones in cancers has been discussed in observational studies; however, the causal relationship between them remains controversial.
METHODS
The SNPs associated with hypothyroidism and hyperthyroidism were selected from a FinnGen biobank of 342,499 (190,879 females and 151,620 males) Finnish adult subjects. Data from the Thyroidomics Consortium on 72,167 individuals were used to assess genetically determined thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Lung cancer, lung adenocarcinoma and squamous cell lung cancer GWAS data from the International Lung Cancer Consortium(ILCCO). Six different Mendelian randomization (MR) Methods, including Inverse variance weighted (IVW), MR-Egger, Simple mode, MR-Pleiotropy Residual Sum and Outlier methods (MR-PRESSO), Weighted mode and Weighted median were used to Two-Sample MR analysis. IVW was used as the primary estimate. Sensitivity analyses were examined via four aspects (Cochran's Q-test, MR Egger intercept analysis, Funnel plot and Leave-one-out sensitivity test).
RESULTS
The OR of hypothyroidism on lung cancer was 0.918 (95% CI, 0.859-0.982; p = 0.013) in MR analysis with IVW method. No evidence for effects of hyperthyroidism, TSH and FT4 on lung cancer risk was found via six MR methods. Meanwhile, there was no evidence for effects of lung cancer on hypothyroidism through six MR methods. Lung adenocarcinoma and squamous cell lung carcinoma were further analyzed on the basis of lung cancer. The OR of hypothyroidism on lung adenocarcinoma was 0.893(95% CI, 0.813-0.981; p = 0.019), the OR of hypothyroidism on squamous cell lung cancer was 0.888(95%CI,0.797-0.990, p = 0.032) in MR analysis with IVW method.
CONCLUSION
In summary, hypothyroidism genetically had a protective causal association with lung cancer. Furthermore, hypothyroidism had protective effects both on lung adenocarcinoma and squamous cell lung cancer. Further work is needed to elucidate the potential mechanisms.
背景
甲状腺激素在癌症中的作用在观察性研究中已有讨论；然而，它们之间的因果关系仍存在争议。
方法
从 342499 名（190879 名女性和 151620 名男性）芬兰成年受试者的 FinnGen 生物库中选择与甲状腺功能减退症和甲状腺功能亢进症相关的 SNP。使用甲状腺组学联盟的数据评估遗传决定的促甲状腺激素（TSH）和游离甲状腺素（FT4）。国际肺癌联盟（ILCCO）的肺癌、肺腺癌和鳞状细胞肺癌 GWAS 数据。使用 6 种不同的孟德尔随机化（MR）方法，包括逆方差加权（IVW）、MR-Egger、简单模式、MR-Pleiotropy Residual Sum and Outlier 方法（MR-PRESSO）、加权模式和加权中位数，进行两样本 MR 分析。IVW 被用作主要估计。通过四个方面（Cochran's Q 检验、MR Egger 截距分析、漏斗图和Leave-one-out 敏感性测试）进行敏感性分析。
结果
在 IVW 方法的 MR 分析中，甲状腺功能减退症与肺癌的比值比（OR）为 0.918（95%CI，0.859-0.982；p=0.013）。通过 6 种 MR 方法未发现甲状腺功能亢进症、TSH 和 FT4 对肺癌风险的影响证据。同时，通过 6 种 MR 方法也未发现肺癌对甲状腺功能减退症的影响证据。在肺癌的基础上，进一步分析了肺腺癌和鳞状细胞肺癌。在 IVW 方法的 MR 分析中，甲状腺功能减退症与肺腺癌的比值比（OR）为 0.893（95%CI，0.813-0.981；p=0.019），甲状腺功能减退症与鳞状细胞肺癌的比值比（OR）为 0.888（95%CI，0.797-0.990，p=0.032）。
结论
总之，甲状腺功能减退症与肺癌存在保护性因果关联。此外，甲状腺功能减退症对肺腺癌和鳞状细胞肺癌均有保护作用。需要进一步的研究来阐明潜在的机制。
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