Assessing the causal association between 731 immunophenotypes and the risk of colorectal cancer: a Mendelian randomization study.

Background: Emerging research suggested a potential role of immune cells in colorectal cancer (CRC) development. However, the causal relationship between immune phenotypes and CRC remains elusive. Hence, this two-sample Mendelian randomization (MR) study aimed to explore the causal association.

Methods: In this study, a bidirectional, two-sample MR analysis and multivariate MR was conducted, leveraging public genetic data. Four types of immune phenotypes were employed. A comprehensive sensitivity analysis was carried out to validate the robustness, heterogeneity, and horizontal pleiotropy of the results, with Bonferroni correction applied for accurate interpretation.

Results: It was revealed that four immune cell phenotypes were significantly associated with CRC risk. Specifically, lymphocyte % leukocyte in the T-cell/B-cell/NK-cell (TBNK) group (odds ratio (OR) = 1.0013, 95% confidence interval (CI): 1.0005-1.0017, P = 0.0003, P_Bonferroni = 0.011) and CD3 on CM CD8br in the maturation stages of T cell group (OR = 1.0014, 95% CI: 1.0006-1.0022, P = 0.0007, P_Bonferroni = 0.023) were positively correlated with the risk of CRC. Conversely, DN (CD4^-CD8^-) %leukocyte in the TBNK group (OR = 0.9990, 95% CI: 0.9984-0.9997, P = 0.0020, P_Bonferroni = 0.063) and herpesvirus entry mediator (HVEM) on CD8br in the maturation stages of T cell group (OR = 0.9989, 95% CI: 0.9982-0.9997, P = 0.00431, P_Bonferroni = 0.137) exhibited a negative association with the risk of CRC. This study did not detect any statistically significant impact of CRC on immune phenotypes.

Conclusions: This study inferred an association between immune cells and CRC risk. Nevertheless, further clinical and experimental studies are warranted to validate these findings and elucidate the underlying mechanisms.