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The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the  IL13  rs1295686A/A  genotype had an increased risk of AML ( P  Corr  = 0.0144) whereas carriers of the  VEGFA  rs25648T  allele had a decreased risk of developing the disease ( P  Corr  = 0.00086). In addition, we found an association of the  IL8  rs2227307  SNP with a decreased risk of developing AML that remained marginally significant after multiple testing ( P  Corr  = 0.072). Functional experiments suggested that the effect of the  IL13  rs1295686  SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the  IL8  rs2227307  SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that  IL13 ,  VEGFA  and  IL8  SNPs play a role in modulating AML risk.

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium