Causal association between immune cell phenotypes and colorectal cancer: a two-sample bidirectional Mendelian randomization analysis

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Increasing evidence suggests that alterations in the immune system may play a pivotal role in the initiation and progression of CRC. However, the precise causal relationship between specific immune cell phenotypes and CRC remains incompletely understood. Elucidating this connection may unveil novel therapeutic targets for the treatment of CRC.

To explore the causal relationship between immune cell phenotypes and CRC, we conducted a comprehensive bidirectional Mendelian randomization (MR) analysis. Genetic variants were utilized as instrumental variables (IVs), with the inverse variance weighting (IVW) method employed to assess the effect of specific immune cell phenotypes on CRC risk. Sensitivity analysis were performed to evaluate the robustness of our findings, while heterogeneity analysis were conducted to minimize the potential impact of pleiotropy.

Our MR analysis revealed potential causal associations between various immune phenotypes and CRC. Specifically, 34 immune cell types were found to be potentially causally associated with colon cancer, while 29 immune cell types showed a potential causal relationship with rectal cancer. Sensitivity analysis further confirmed the robustness of these associations, suggesting that these immune cell phenotypes may play a significant role in the development of CRC.

Our study provides evidence for a causal relationship between immune cell phenotypes and CRC. These findings suggest that immune cell characteristics may serve as potential biomarkers for CRC and could represent novel therapeutic targets. However, further experimental research is needed to explore the underlying mechanisms in greater detail and to validate the clinical applicability of these findings.