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炎症细胞因子与肺癌之间的因果关系:一项两样本双向孟德尔随机化研究。

The causal relationship between inflammatory cytokines and lung cancer: a two-sample bidirectional mendelian randomization study.

作者信息

Zhao Kaiyang, Wang Ning, He Peiyan, Shi Wenhan, Fan Rongke, Peng Shengxian

机构信息

Department of Thoracic Surgery, The 1 st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.

Xinxiang Medical University, Xinxiang, 453000, China.

出版信息

Discov Oncol. 2025 Aug 22;16(1):1592. doi: 10.1007/s12672-025-03256-x.

Abstract

OBJECTIVE

The objective is to investigate the causal link between inflammatory cytokines and lung cancer through the application of a two-sample bidirectional Mendelian randomization (MR) approach.

METHOD

This study gathered data from genome-wide association studies (GWAS), focusing on 91 inflammatory cytokines associated with lung cancer. The investigation into the causal link between inflammatory cytokines and lung cancer was performed utilizing several methods, including the inverse variance weighted (IVW) approach, weighted median (WM) method, MR Egger regression, weighted mode, and simple mode. The IVW method served as the primary evaluative metric, while various sensitivity analyses were carried out to assess the heterogeneity and horizontal pleiotropy of the MR outcomes.

RESULT

A total of 3 Inflammatory cytokines were identified as having a positive causal association with lung cancer. Among these, CCL25 (OR = 1.060, 95% CI 1.020-1.102) is a risk factor for lung cancer, increasing the risk of developing the disease; while GDNF (OR = 0.872, 95% CI 0.762-1.000) and IL-18 (OR = 0.852, 95% CI 0.781-0.930) are protective factors for lung cancer, reducing the risk of developing the disease.

CONCLUSION

This research indicates a possible causal link between inflammatory cytokines and lung cancer, highlighting the involvement of several inflammatory cytokines in the disease's development. It offers fresh perspectives on how inflammatory cytokines mediate the pathogenesis of lung cancer, holding great importance for prevention, treatment, and symptom enhancement of the disease.

摘要

目的

通过应用两样本双向孟德尔随机化(MR)方法,研究炎症细胞因子与肺癌之间的因果关系。

方法

本研究收集了全基因组关联研究(GWAS)的数据,重点关注与肺癌相关的91种炎症细胞因子。利用多种方法对炎症细胞因子与肺癌之间的因果关系进行了研究,包括逆方差加权(IVW)法、加权中位数(WM)法、MR-Egger回归、加权模式和简单模式。IVW法作为主要评估指标,同时进行了各种敏感性分析,以评估MR结果的异质性和水平多效性。

结果

共鉴定出3种炎症细胞因子与肺癌呈正因果关联。其中,CCL25(OR = 1.060,95%CI 1.020 - 1.102)是肺癌的危险因素,增加了患肺癌的风险;而GDNF(OR = 0.872,95%CI 0.762 - 1.000)和IL-18(OR = 0.852,95%CI 0.781 - 0.930)是肺癌的保护因素,降低了患肺癌的风险。

结论

本研究表明炎症细胞因子与肺癌之间可能存在因果关系,突出了几种炎症细胞因子在疾病发展中的作用。它为炎症细胞因子如何介导肺癌发病机制提供了新的视角,对该疾病的预防、治疗和症状改善具有重要意义。

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