Investigating the causal relationship between immune cells and colorectal cancer risk using bidirectional and multivariable Mendelian randomization analysis.

Objectives: This study explores the relationship between immune recognition diversity and colorectal cancer (CRC) risk using a bidirectional Mendelian randomization approach.

Methods: Genetic data from 731 immune cell types were analyzed, with data sourced from the IEU and FinnGen databases and CRC data from genome-wide association studies on the Finnish population. Forward and reverse Mendelian randomization analyses were conducted, with sensitivity analyses to assess pleiotropic effects.

Results: Analyses revealed a significant association between increased Effector Memory CD4 and CD8 T cells and higher CRC risk (odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.04-1.18, p = .0008). Conversely, elevated CD45 on natural killer T cells was associated with a lower CRC risk (OR = 0.93, 95% CI = 0.88-0.98, p = .0095), indicating a protective effect. Sensitivity analyses confirmed no pleiotropic effects.

Conclusions: These findings highlight specific immune cells' roles in CRC pathogenesis, suggesting potential avenues for immune-targeted therapies and CRC prevention. Given the rising global incidence of CRC, understanding immune cell roles is crucial for advancing effective treatments.