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探讨炎症细胞因子与结直肠癌之间的因果关联：两样本孟德尔随机化研究。

Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian randomization study.

机构信息

Department of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China.

Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, P.R. China.

出版信息

Medicine (Baltimore). 2024 Nov 1;103(44):e40230. doi: 10.1097/MD.0000000000040230.

DOI:10.1097/MD.0000000000040230
PMID:39496027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11537590/
Abstract

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and the risk of colorectal cancer, but the findings have been inconsistent. In this study, we employed a 2-sample Mendelian randomization (MR) analysis, primarily using the inverse variance weighted approach, to investigate the causal relationship between inflammatory cytokines and CRC. The forward MR analysis revealed a positive association between higher levels of interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor (OR: 1.44, P = .001), and MIG (OR: 1.23, P = .040) with an increased risk of rectal cancer. Conversely, higher levels of macrophage colony-stimulating factor (OR: 0.80, P = .010) may potentially decrease the risk of colon cancer. In the reverse MR analysis, it was found that rectal cancer is linked to higher levels of IL-1b (OR: 0.93, P = .022), IL-1ra (OR: 0.90, P = .001), IL-5 (OR: 0.93, P = .022), IL-9 (OR: 0.93, P = .017), and TNF-a (OR: 0.91, P = .003). Additionally, colon cancer is associated with elevated levels of FGF-Basic (OR: 1.10, P = .028). Consistent results were also found in MR-Egger, weighted median, and weighted mode analysis. Our study presents novel evidence supporting the causal relationship between inflammatory cytokines and CRC.

摘要

结直肠癌（CRC）是一个重大的全球公共卫生问题。多项观察性研究已经探讨了炎症细胞因子与结直肠癌风险之间的关联，但结果并不一致。在这项研究中，我们采用了两样本孟德尔随机化（MR）分析，主要使用逆方差加权法，研究了炎症细胞因子与 CRC 之间的因果关系。正向 MR 分析显示，白细胞介素（IL）-16（OR：1.37，P=0.002）、血管内皮生长因子（OR：1.44，P=0.001）和 MIG（OR：1.23，P=0.040）水平升高与直肠癌风险增加呈正相关。相反，巨噬细胞集落刺激因子（OR：0.80，P=0.010）水平升高可能降低结肠癌的风险。在反向 MR 分析中，发现直肠癌与较高水平的白细胞介素-1b（OR：0.93，P=0.022）、白细胞介素-1ra（OR：0.90，P=0.001）、白细胞介素-5（OR：0.93，P=0.022）、白细胞介素-9（OR：0.93，P=0.017）和肿瘤坏死因子-a（OR：0.91，P=0.003）相关。此外，结肠癌与碱性成纤维细胞生长因子（FGF-Basic）水平升高有关（OR：1.10，P=0.028）。MR-Egger、加权中位数和加权众数分析也得出了一致的结果。我们的研究提供了新的证据，支持炎症细胞因子与 CRC 之间的因果关系。

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