Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China.
Front Immunol. 2024 Mar 27;15:1336817. doi: 10.3389/fimmu.2024.1336817. eCollection 2024.
Numerous observational studies have indicated that smoking is a substantial risk factor for esophageal cancer. However, there is a shortage of research that delves into the specific causal relationship and potential mediators between the two. Our study aims to validate the correlation between smoking-related traits and esophageal cancer while exploring the possible mediating effects of immune factors.
Initially, we conducted bidirectional univariate Mendelian Randomization (MR) analyses to forecast the causal effects linking smoking-related traits and esophageal cancer. Subsequently, we employed a two-step MR analysis to scrutinize immune cell phenotypes that could mediate these effects. Finally, the coefficient product method was employed to determine the precise mediating impact. Additionally, we have refined our sensitivity analysis to ensure the reliability of the outcomes.
After analysis, Smoking status: Never had a significant negative association with the incidence of esophageal cancer (inverse-variance weighted (IVW) method, p=1.82e-05, OR=0.10, 95%CI=0.040.29). Ever smoked (IVW, p=1.49e-02, OR=4.31, 95%CI=1.3313.94) and Current tobacco smoking (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) showed the promoting effect on the pathogenesis of esophageal cancer. Through further examination, researchers discovered 21 immune cell phenotypes that have a causal relationship with esophageal cancer. After careful screening, two immune cell phenotypes were found to have potential mediating effects. In particular, it was observed that in the case of the preventive effect of Smoking status: Never on esophageal cancer, the absolute count of CD62L plasmacytoid dendritic cells mediated a reduction of 4.21%, while the mediating effect of CD27 in CD20-CD38-B cells was -4.12%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy.
The study provides new evidence for the causal relationship between smoking-related features and esophageal cancer and proposes immune factors with potential mediating effects. However, this finding needs to be further demonstrated by more extensive clinical studies.
大量观察性研究表明，吸烟是食管癌的一个重要危险因素。然而，目前缺乏深入研究吸烟相关特征与食管癌之间的具体因果关系和潜在中介因素。我们的研究旨在验证与吸烟相关特征与食管癌之间的相关性，同时探索免疫因素的可能中介作用。
首先，我们进行了双向单变量孟德尔随机化（MR）分析，以预测与吸烟相关特征和食管癌相关的因果效应。随后，我们采用两步 MR 分析方法研究了可能介导这些效应的免疫细胞表型。最后，采用系数乘积法确定确切的中介影响。此外，我们还进行了敏感性分析以确保结果的可靠性。
经过分析，从不吸烟与食管癌的发病率呈显著负相关（逆方差加权（IVW）法，p=1.82e-05，OR=0.10，95%CI=0.040.29）。曾经吸烟（IVW，p=1.49e-02，OR=4.31，95%CI=1.3313.94）和当前吸烟（IVW，p=1.49e-02，OR=4.31，95%CI=1.33~13.94）均显示出对食管癌发病机制的促进作用。进一步研究发现，有 21 种免疫细胞表型与食管癌有因果关系。经过仔细筛选，发现两种免疫细胞表型具有潜在的中介作用。特别是，在从不吸烟对食管癌的预防作用中，CD62L 型浆细胞样树突状细胞的绝对计数介导了 4.21%的降低，而 CD27 在 CD20-CD38-B 细胞中的中介作用为-4.12%。此外，敏感性分析未发现显著的异质性或水平多效性。
本研究为吸烟相关特征与食管癌之间的因果关系提供了新的证据，并提出了具有潜在中介作用的免疫因素。然而，这一发现需要更多广泛的临床研究进一步证实。
