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

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. 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. In this study, T-cell surface glycoprotein CD6 isoform (OR = 1.247, 95% CI: 1.020-1.524, p = 0.031) and interleukin-24 (OR = 1.679, 95% CI: 1.056-2.669, p = 0.029) were positively associated with MDS risk, while cystatin D (OR = 0.778, 95% CI: 0.642-0.943, p = 0.010) and SIR2-like protein 2 (OR = 0.614, 95% CI: 0.385-0.979, p = 0.041) were negatively associated. These findings were stable in the sensitivity analysis. 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.