Mendelian randomization investigation of the causal association between circulating cytokines and colorectal cancer

Abstract Objective To explore the causal relationship between colorectal cancer risk and circulating cytokines and identify potential predictive biomarkers. Methods This study employed a bidirectional Mendelian randomization (MR) analysis based on data from genome-wide association (GWAS) studies of colorectal cancer from people of European ancestry. The genetic variants associated with 41 circulating cytokines exposed were selected as instrumental variables for this experiment. For robustness and consistency of findings, we conducted additional sensitivity analyses and reverse Mendelian randomization assessments. Results The analysis revealed a strong causal relationship between colorectal cancer occurrence and Vascular Endothelial Growth Factor (VEGF), Macrophage Colony Stimulating Factor (MCSF), Interleukin-12p70 (IL-12p70), Interleukin-13(IL-13), Interleukin-10 levels (IL-10) and Interleukin-7 levels (IL-7) and demonstrated partial consistency. Sensitivity analyses indicated that IL-12p70, IL-7 and VEGF are potential colorectal cancer predictive biomarkers. Conclusion This Mendelian randomized study offers valuable insights into the causal relationships between specific circulating cytokines and colorectal cancer risk. The identified cytokines may serve as predictive biomarkers, enabling the development of novel diagnostic, preventive, and therapeutic approaches, but further experimental validation of their potential as diagnostic biomarkers or cancer-related pharmacological targets is necessary.