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 = 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 = 0.023) were positively correlated with the risk of CRC. Conversely, DN (CD4CD8) %leukocyte in the TBNK group (OR = 0.9990, 95% CI: 0.9984-0.9997, P = 0.0020, P = 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 = 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.