A Mendelian randomized study on the correlation between 91 inflammatory protein levels and the risk of acute myeloid leukemia

Objective The study aims to analyze the correlation between circulating inflammatory proteins and the risk of acute myeloid leukemia (AML). Methods AML data were obtained from the FinnGen alliance as the outcome. The Genome-wide Association Studies (GWAS) data of 91 circulating inflammatory proteins were used as exposure factors. Mendelian randomization (MR) analysis was conducted to evaluate the effects of 91 circulating inflammatory proteins on the risk of AML. Inverse Variance Weighted (IVW) was used as the main analysis method, and the MR-Egger and Weighted Median (WM) methods were used to further strengthen the results. In addition, sensitivity analysis was used to evaluate the stability and reliability of the results. Results Among the 91 circulating inflammatory proteins, 8 were causally associated with the occurrence of AML (P<0.05). Specifically, higher levels of artemin (ARTN) (OR=0.458 3, 95% CI: 0.219 0-0.959 1), interleukin (IL)-2 receptor β (OR=0.2347, 95% CI: 0.094 1-0.585 3), sirtuin-2 (SIRT2) (OR=0.310 4, 95%CI: 0.138 0-0.698 2), and signal-transducing adaptor molecule binding protein (STAMPB) (OR=0.289 0, 95% CI: 0.104 9-0.796 1) were associated with a reduced risk of AML. In contrast, higher levels of CD6 (OR=3.269 3, 95% CI: 1.285 3-8.315 9), C-X-C motif chemokine ligand 5 (CXCL5) (OR=1.694 6, 95% CI: 1.013 4-2.833 6), IL-15 receptor α (OR=1.572 9, 95% CI: 1.050 0-2.344 8), and matrix metalloproteinase (MMP)-10 (OR=1.882 0, 95% CI: 1.061 4-3.337 1) were associated with an increased risk of AML. Sensitivity analysis using Cochran’s Q test (P>0.05) and MR-Egger regression test (P>0.05) showed no heterogeneity or pleiotropy in the single nucleotide polymorphisms (SNPs) of inflammatory proteins. Conclusions The Mendelian randomization study suggests that circulating inflammatory proteins ARTN, IL-2β, SIRT2, STAMPB, CD6, CXCL-5, IL-15α, and MMP-10 are causally associated with the risk of AML, which provides valuable insights for future research on the pathological mechanism of AML.