代谢因素会增加甲状腺癌的风险吗？一项孟德尔随机化研究。

Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study.

机构信息

Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Cancer Institute, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Front Endocrinol (Lausanne). 2023 Sep 15;14:1234000. doi: 10.3389/fendo.2023.1234000. eCollection 2023.

DOI:10.3389/fendo.2023.1234000

PMID:37780617

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10541021/

Abstract

BACKGROUND

Epidemiological studies emphasize the link between metabolic factors and thyroid cancer. Using Mendelian randomization (MR), we assessed the possible causal impact of metabolic factors on thyroid cancer for the first time.

METHODS

Summary statistics for metabolic factors and thyroid cancer were obtained from published Genome-wide association studies. The causal relationships were assessed using the inverse-variance weighted (IVW) method as the primary method through a two-sample Mendelian Randomization (MR) analysis. To account for the potential existence of horizontal pleiotropy, four additional methods were employed, including Mendelian Randomization-Egger (MR-Egger), weighted median method (WM), simple mode, and weighted mode method. Given the presence of interactions between metabolic factors, a multivariable MR analysis was subsequently conducted.

RESULTS

The results showed there was a genetic link between HDL level and protection effect of thyroid cancer using IVW (OR= 0.75, 95% confidence intervals [CIs] 0.60-0.93, p=0.01) and MR-Egger method (OR= 0.70, 95% confidence intervals [CIs] 0.50- 0.97, p=0.03). The results remained robust in multivariable MR analysis for the genetic link between HDL level and protection effect of thyroid cancer (OR= 0.74, 95% confidence intervals [CIs] 0.55-0.99, p=0.04).

CONCLUSIONS

This study suggests a protection role for HDL on thyroid cancer. The study findings provide evidence for the public health suggestion for thyroid cancer prevention. HDL's potential as a pharmacological target needs further validation.

摘要

背景

流行病学研究强调代谢因素与甲状腺癌之间的联系。本研究首次使用孟德尔随机化（Mendelian randomization，MR）评估代谢因素对甲状腺癌的可能因果影响。

方法

从已发表的全基因组关联研究中获取代谢因素和甲状腺癌的汇总统计数据。使用逆方差加权（inverse-variance weighted，IVW）法作为主要方法，通过两样本 Mendelian Randomization（MR）分析评估因果关系。为了考虑潜在的水平多效性，采用了 Mendelian Randomization-Egger（MR-Egger）、加权中位数法（weighted median method，WM）、简单模式和加权模式法等四种额外方法。鉴于代谢因素之间存在相互作用，随后进行了多变量 MR 分析。

结果

结果表明，使用 IVW（OR=0.75，95%置信区间 [CI] 0.60-0.93，p=0.01）和 MR-Egger 方法（OR=0.70，95%置信区间 [CI] 0.50-0.97，p=0.03）发现 HDL 水平与甲状腺癌保护作用之间存在遗传关联。在多变量 MR 分析中，HDL 水平与甲状腺癌保护作用之间的遗传关联仍然稳健（OR=0.74，95%置信区间 [CI] 0.55-0.99，p=0.04）。