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

ObjectivesThis study explores the relationship between immune recognition diversity and colorectal cancer (CRC) risk using a bidirectional Mendelian randomization approach.MethodsGenetic 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.ResultsAnalyses 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.ConclusionsThese 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.