title: MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group.
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.
  
  
  METHODS
  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.
authors.affiliation: Division of Hematology Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. christine.phillips@cchmc.org
authors.forename: Christine L
authors.initials: CL
authors.lastname: Phillips
authors.forename: Robert
authors.initials: R
authors.lastname: Gerbing
authors.forename: Todd
authors.initials: T
authors.lastname: Alonzo
authors.forename: John P
authors.initials: JP
authors.lastname: Perentesis
authors.forename: Isaac T W
authors.initials: IT
authors.lastname: Harley
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.forename: Deepika
authors.initials: D
authors.lastname: Bhatla
authors.forename: Gretchen
authors.initials: G
authors.lastname: Radloff
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2