SNPs may be useful biomarkers for AML risk
Single-nucleotide polymorphisms (SNPs) on the IL13 and VEGFA genes are associated with the risk of developing acute myeloid leukaemia (AML), reports a recent study.
The two-stage genetic association study included a discovery population of 2,027 Europeans (338 AML patients and 1,689 controls) and a replication population (316 AML patients and 1,788 controls).
In the discovery population, 11 immunoregulatory SNPs were found to be associated with AML risk (p<0.05). For instance, carriers of the IFNGR2rs1059293T allele and the IL4rs2243248G/G, IL13rs20541T/T, IL13rs1295686A/A, and VEGFArs998584T/T genotypes were at greater risk of developing AML. Notably, each copy of the IL4rs2243268C increased the risk of AML by 1.31-fold.
Carriers of the IL8rs2227307G and VEGFArs25648T, on the other hand, were significantly protected from AML development.
In the pooled analysis of both discovery and replication cohorts, IL13rs1295686 genotype remained significantly correlated with a higher AML risk (p=0.0144), while carriers of the IL8rs2227307G allele saw marginal protection against the disease (p=0.072). Similarly, those with the VEGFArs25648T was found to be strongly and significantly associated with a lower risk of AML (p=0.00086).
In vitro experiments showed that the three genetic biomarkers uncovered in the present study may play a role in the modulation of innate and adaptive immune responses. This suggests that they are potential “clinical targets for enhancement of the antileukaemic effects of immune cells,” the researchers said.