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

Leuk Res. 2010 Apr;34(4):492-7. doi: 10.1016/j.leukres.2009.08.007. Epub 2009 Sep 16.

Abstract

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 gamma/alpha isoforms (p=0.04), which possibly explains its association with reduced event-free survival and overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Female
  • Gene Frequency
  • Genetic Linkage
  • Humans
  • Infant
  • Male
  • Outcome Assessment, Health Care
  • Polymorphism, Single Nucleotide*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prognosis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, Glucocorticoid / genetics*
  • Survival Analysis

Substances

  • NR3C1 protein, human
  • Protein Isoforms
  • Receptors, Glucocorticoid