Mendelian randomization study explores the peripheral immunological characteristics of colorectal cancer - Analysis - Open Access

Sep 30, 2026

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Background: Colorectal cancer (CRC) is a frequent malignancy worldwide, yet the immunological mechanisms driving CRC pathogenesis remain unclear. Objective: Determine causal relationships between immune cell phenotype variation and CRC using a two-sample bidirectional Mendelian randomization framework. Methods combine inverse variance weighted as the primary approach with MR-Egger, weighted median, and mode-based sensitivity analyses, plus Cochran’s Q, MR-Egger intercept, MR-PRESSO, leave-one-out, and funnel plots. Results support bidirectional causal links between specific immune traits and CRC risk.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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Abstract

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Yuan et al. Discover Oncology (2026) 17:19 [https://doi.org/10.1007/s12672-025-04250-z](https://doi.org/10.1007/s12672-025-04250-z) Discover Oncology ANALYSIS Open Access Mendelian randomization study explores the peripheral immunological characteristics of colorectal cancer Chendong Yuan1,2†, Xufeng Shu1,2†, Xiaoqiang Wang1,2†, Zhenzhen Hu3* and Zhigang Jie1,2* †Chendong Yuan, Xufeng Shu and Xiaoqiang Wang have contributed equally to this work. *Correspondence: Zhenzhen Hu[ndyfyhzz9989@163.com](ndyfyhzz9989@163.com)[ ](ndyfyhzz9989@163.com)Zhigang Jie[ndyfy00524@ncu.edu.cn](ndyfy00524@ncu.edu.cn)[ ](ndyfy00524@ncu.edu.cn)1Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, N0.17, Yongwai main Street, Nanchang 330006, Jiangxi, China 2Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, N0.17, Yongwai main Street, Nanchang 330006, Jiangxi, China 3Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, N0.17, Yongwai main Street, Nanchang 330006, Jiangxi, China Abstract Background Colorectal cancer (CRC) is one of the most common malignancies worldwide. However, the immunological mechanisms underlying CRC pathogenesis remain unclear. This study aims to elucidate the causal relationships between immune cell phenotypes and CRC. Methods Based on publicly available genetic data from Genome-wide association studies, we conducted a two-sample bidirectional Mendelian randomization analysis to ascertain the causal relationship between 731 immune cell features and CRC. The inverse variance weighted method was employed as the primary causal analysis approach, complemented by four additional methods: MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and the funnel plot. Results Forward MR analysis identified seven immune phenotypes with significant causal effects on CRC risk, including CD11b on basophils, CX3CR1 on CD14-CD16 + monocytes, and Activated & Resting Treg %CD4+ . Reverse MR revealed that CRC significantly influenced the levels of seven immune traits, such as CD27 on memory B cells and CD3 on CD4 + T cells. These associations remained robust across multiple MR methods and sensitivity tests. Conclusion Our findings provide genetic evidence of bidirectional causal links between specific immune cell phenotypes and CRC. These insights may contribute toa better understanding ofCRC immunopathogenesis and inform immunotherapeutic strategies. Keywords Colorectal cancer, Immune cells, Mendelian randomization, Immune microenvironment, Causal relationship 1 Introduction Colorectal cancer (CRC) is ranked as the third most prevalent form of cancer globally and constitutes the second leading cause of cancer-related mortality. In 2018, it was estimated that there were approximately 1.8 million new cases of CRC worldwide, © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission d

FAQs

What question does the study address about colorectal cancer?

The study investigates the causal relationships between immune cell phenotypes and colorectal cancer, addressing how immune characteristics may contribute to CRC pathogenesis.

How was causality assessed in the research?

It used a two-sample bidirectional Mendelian randomization analysis based on publicly available genetic data, with inverse variance weighted as the primary method and several complementary MR approaches.

What were the key findings regarding immune traits and CRC?

Forward MR identified seven immune phenotypes with significant causal effects on CRC risk, while reverse MR showed CRC influenced seven immune traits, with robustness across multiple MR methods and sensitivity tests.

Sep 30, 2026

Upload by James