Mendelian randomization study explores the peripheral immunological characteristics of colorectal cancer

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.

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.

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.

Our findings provide genetic evidence of bidirectional causal links between specific immune cell phenotypes and CRC. These insights may contribute to a better understanding of CRC immunopathogenesis and inform immunotherapeutic strategies.