Causal relationship between circulating cytokines and myelodysplastic syndrome: a Mendelian randomization study

Objective: Current research links cytokines to cancer occurrence and development. This study used Mendelian randomization (MR) to examine the causal relationship between circulating cytokines and Myelodysplastic syndrome (MDS) onset. Methods: We analyzed 91 circulating cytokines as exposures and MDS genome-wide association study (GWAS) summary statistics as outcomes using a two-sample MR approach, with primary results derived from the IVW method. Robustness was assessed through heterogeneity, horizontal pleiotropy, and leave-one-out analyses. Results: In this study, T-cell surface glycoprotein CD6 isoform (OR = 1.247, 95% CI: 1.020-1.524, <i>p</i> = 0.031) and interleukin-24 (OR = 1.679, 95% CI: 1.056-2.669, <i>p</i> = 0.029) were positively associated with MDS risk, while cystatin D (OR = 0.778, 95% CI: 0.642-0.943, <i>p</i> = 0.010) and SIR2-like protein 2 (OR = 0.614, 95% CI: 0.385-0.979, <i>p</i> = 0.041) were negatively associated. These findings were stable in the sensitivity analysis. Conclusions: This MR study provides preliminary evidence that the genetically predicted levels of four circulating cytokines may influence the risk of developing MDS. The specific mechanisms require further exploration.