Causal effects of vitamin D on leukemia risk: insights from two-sample Mendelian randomization analysis

Abstract Background: vitamin D plays a crucial role in immune regulation, anti-inflammatory processes, and tumor suppression, but its relationship with leukemia risk remains unclear. This study aims to evaluate the causal relationship between vitamin D levels and the risk of different types of leukemia through a two-sample Mendelian randomization (MR) analysis. Methods: data from large-scale genome-wide association studies (GWAS) were used, and genetic variants associated with vitamin D were selected as instrumental variables. The relationship between vitamin D levels and the risk of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML) was examined. The inverse variance weighted (IVW) method was applied as the primary analytical approach. Heterogeneity was assessed through Cochran's Q test, pleiotropy was evaluated using the MR-Egger intercept, and sensitivity analyses were performed to ensure the robustness of the results. Results: MR analysis showed a significant inverse association between serum 25-hydroxyvitamin D levels and the risk of CML (OR = 0.44, 95 % CI: 0.25-0.78, p = 0.005), suggesting a potential protective effect of vitamin D against CML. No significant causal relationships were found between vitamin D levels and the risks of AML, ALL, or CLL. Sensitivity analyses supported the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Conclusion: the findings indicate that higher vitamin D levels may reduce the risk of CML, while the effects on other types of leukemia require further investigation. The potential role of vitamin D in leukemia prevention warrants more mechanistic studies and clinical validation.