Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2024-06-16 DOI:10.1016/j.cyto.2024.156680

Zishen Liu, Yingying Zheng, Mengqi Yuan, Ganlin Zhang, Guowang Yang

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引用次数: 0

Abstract

Background

In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations.

Methods

We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13.

Results

By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001–1.204, P = 0.047; IL-2, OR = 1.112, 95 % CI 1.009–1.225, P = 0.032; IL-13, OR = 1.068, 95 % CI 1.007–1.132, P = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010–1.220, P = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL-13 targets in lung cancer.

Conclusion

The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cancer prediction models and targets for anti-tumor therapy.

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CTACK、IL-2 和 IL-13 与肺癌风险增加的关系：孟德尔随机研究

背景近年来，有相关研究报告称，炎性细胞因子与癌症的发生有关。然而，与肺癌的相关性尚不明确。方法我们通过开放数据库获得了炎性细胞因子的单核苷酸多态性（SNPs），并通过 IEU OpenGWAS 项目获得了肺癌（欧洲和东亚）的 SNPs。反方差加权（IVW）磁共振分析用于确定暴露和结果的因果关系。此外，还使用加权中位数和 MR-Egger 回归进行了补充分析。之后，还进行了敏感性分析以检验稳健性。结果通过 IVW 方法，我们发现 CTACK、IL-2 和 IL-13 与欧洲人群肺癌风险增加有关（CTACK，OR = 1.098，95 % CI 1.001-1.204，P = 0.047；IL-2，OR = 1.112，95 % CI 1.009-1.225，P = 0.032；IL-13，OR = 1.068，95 % CI 1.007-1.132，P = 0.029），而在东亚人群中，只有 IL-13 与肺癌风险增加有关（IL-13，OR = 1.110，95 % CI 1.010-1.220，P = 0.030）。加权中位数和MR-Egger回归方法与IVW效应大小方向相同。此外，使用 MR-Egger 截距作为敏感性分析，也没有发现多向性的证据。结论研究结果表明，炎性细胞因子 CTACK、IL-2 和 IL-13 会增加罹患肺癌的风险。目前缺乏针对这三个靶点的药物适应症。我们探讨了炎性细胞因子与肺癌之间的因果关系，为未来的癌症预测模型和抗肿瘤治疗靶点提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.