Polymorphisms in glucocorticoid receptor gene and the outcome of childhood acute lymphoblastic leukemia (ALL)

Childhood acute lymphoblastic leukemia patients (n = 310) were analyzed for four SNPs in the NR3C1 gene. Polymorphisms −627A/G, intron 2 +646C/G and 9bT/C were all associated with reduced event-free survival. Haplotypes composed of AGT alleles at these loci and tagged by the intron 2 +646G variant also associated with lower event-free survival (p = 0.03). The progressive impact of this haplotype on outcome was seen with two copies associated with reduced overall survival (p = 0.05). Quantitative mRNA analysis in lymphoblastoid cell lines showed that carriers of the AGT haplotype had a higher ratio of GR γ/α isoforms (p = 0.04), which possibly explains its association with reduced event-free survival and overall survival.