Ontology highlight
ABSTRACT: Background
The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li-Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro.Procedure
We genotyped children (n = 575) with de novo acute myeloid leukemia (AML) treated on three Children's Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population.Results
The variant G/G genotype was associated with an increased susceptibility to AML (OR 1.5; P = 0.049). However, the presence of the variant allele at SNP309 did not modify disease response or toxicity in children treated on CCG protocols 2941/2961.Conclusions
The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy.
SUBMITTER: Phillips CL
PROVIDER: S-EPMC2915901 | biostudies-literature | 2010 Aug
REPOSITORIES: biostudies-literature
Phillips Christine L CL Gerbing Robert R Alonzo Todd T Perentesis John P JP Harley Isaac T W IT Meshinchi Soheil S Bhatla Deepika D Radloff Gretchen G Davies Stella M SM
Pediatric blood & cancer 20100801 2
<h4>Background</h4>The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li-Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro ...[more]