Discov Oncol. 2025 May 29;16(1):944. doi: 10.1007/s12672-025-02819-2.
ABSTRACT
BACKGROUND: Cervical cancer remains a significant global health concern, with immune system regulation potentially playing a crucial role in disease development. This study investigates potential causal relationships between genetic variants associated with immune cell populations and cervical cancer risk.
METHODS: We employed multiple Mendelian randomization (MR) approaches inverse-variance weighted, MR-Egger, simple median, and weighted median methods to evaluate genetic instrumental variables linked to various T-cell and B-cell subtypes. Differential gene expression was analyzed using single-cell RNA sequencing, while forest plots, scatter plots, and funnel plots facilitated comprehensive MR analysis.
RESULTS: Forest plots consistently demonstrated odds ratios clustered tightly around 1.000 (range: 0.998-1.001), despite some variants reaching statistical significance (p < 0.05). MR analysis of CD69 + LGALS3A + regulatory T-cells, CD8 + T-cell populations, and CD20 + B-cells revealed only weak associations with cervical cancer susceptibility. Comparative analysis across different MR methodologies produced consistent results with minimal horizontal pleiotropy bias.
CONCLUSION: While immune cell genetic factors may contribute to cervical cancer development, their causal effects appear modest. These findings suggest that genetic predisposition through immune cell regulation likely plays a supplementary rather than primary role in cervical cancer pathogenesis.
PMID:40439950 | DOI:10.1007/s12672-025-02819-2
