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

Abstract

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.

Functional Genetic Variants in ATG10 Are Associated with Acute Myeloid Leukemia

“…Demographic characterization of the cohorts is detailed in Table 1 . Cohort 1 consisted of 665 Spanish subjects from the NuCLEAR consortium [ 31 ] comprising 309 AML patients and 356 healthy subjects. Gender balance was observed in cohort 1 (χ 2 test, p = 0.612), while age distribution was statistically different between AML cases and healthy controls (56 ± 6 and 58 ± 17 years mean age, respectively, p < 0.05).…”

“…Cohort 1 consisted of 665 Spanish subjects, including 309 AML subjects and 356 healthy subjects that were ascertained through the NuCLEAR consortium [ 31 ]. All ethical issues concerning this cohort are described in [ 31 ]. Cohort 2 included 46 healthy Portuguese subjects.…”

Immune checkpoint‐related gene polymorphisms are associated with acute myeloid leukemia

“…Single nucleotide polymorphisms (SNPs) are the most common type of genetic variants in humans and increasing research reports their important function in human diseases 12,13 . In AML, the AA genotype of interleukin‐13 (IL13) (rs1295686) increased the risk of AML, while IL8 (rs2227307) decreased the risk of AML 14 . The GG genotype of rs6887695 of IL‐12A decreased the survival of AML patients 15 .…”

“… 12 , 13 In AML, the AA genotype of interleukin‐13 (IL13) (rs1295686) increased the risk of AML, while IL8 (rs2227307) decreased the risk of AML. 14 The GG genotype of rs6887695 of IL‐12A decreased the survival of AML patients. 15 TNF‐α and IL‐10 are associated with the susceptibility to AML.…”