Casual association between circulating cytokines and colorectal cancer: A Mendelian Randomization Study

Background: Colorectal cancer (CRC) represents a significant health issue globally, and comprehending it's molecular basis is crucial for developing effective intervention strategies.This research explores the causal links among cytokines, and CRC through a Mendelian Randomization (MR) framework.Methods: A comprehensive two-sample Mendelian randomization (MR) analysis was performed in this research.In summary, publicly accessible genetic data were used to explore the causal relationship between 41 cytokines, 91 cytokines and with colorectal cancer (CRC).For MR analysis, the inverse variance weighted (IVW) method and weighted medians were applied, while to evaluate heterogeneity and pleiotropy, sensitivity analyses were performed.Results: Our results demonstrated a significant association between the likelihood of developing of colorectal cancer (CRC) and the concentration of the T-cell surface membrane glycoprotein CD5 [odds ratio (OR) = 0.746, 95% confidence interval (CI) = 0.605-0.920,p = 0.006], C-C motif chemokine 4 [OR = 0.886, 95% CI = 0.810-0.969,p = 0.008], CUB domain-containing protein 1 [OR = 0.845, 95% CI = 0.738-0.968,p = 0.0157], TNF-related apoptosis-inducing ligand [OR = 0.858, 95% CI = 0.755-0.975,p = 0.018], Interleukin-6 [OR = 0.719, 95% CI = 0.570-0.9058,p = 0.005], and Tumor necrosis factor beta [OR = 1.102, 95% CI = 1.015-1.197,p = 0.019].Conclusion: These findings open new avenues for additional research into the clinical use of T-cell surface membrane glycoprotein CD5, C-C motif chemokine 4, CUB domain-containing protein 1, TNF-related apoptosis-inducing ligand, Interleukin-6, and Tumor necrosis factor beta in colorectal cancer, presenting hopeful opportunities for diagnosis and therapy.