title: FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.
abstract: OBJECTIVE
  FAS is a cell surface receptor involved in apoptotic signal transmission. Deregulation of this pathway results in down-regulation of apoptosis and subsequent persistence of a malignant clone. A single nucleotide polymorphism resulting in guanine-to-adenine transition in the FAS promoter region (position -1377) is thought to reduce stimulatory protein 1 transcription factor binding and decrease FAS expression. Previous work has shown increased risk of developing acute myeloid leukemia (AML) in adult patients with a variant allele at this site. The same authors have shown that the presence of an adenine residue rather than a guanine residue at -1,377 bp significantly attenuates transcription factor stimulatory protein 1 binding and may contribute to a reduction in FAS expression and ultimately to the enrichment of apoptosis-resistant clones in AML. We hypothesized that FAS genotype by altering susceptibility to apoptosis might affect outcome of childhood AML therapy.
  
  
  METHODS
  Four hundred forty-four children treated for de novo AML on a uniform protocol were genotyped for FAS 1377.
  
  
  RESULTS
  There were no significant differences in overall survival, event-free survival, treatment-related mortality, or relapse rate between patients with FAS 1377GG genotype versus 1377GA/1377AA genotypes.
  
  
  CONCLUSIONS
  FAS 1377 genotype does not alter outcome of de novo AML in children.
authors.affiliation: Division of Hematology/Oncology, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio 45229, USA. parinda.mehta@cchmc.org
authors.forename: Parinda A
authors.initials: PA
authors.lastname: Mehta
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: James S
authors.initials: JS
authors.lastname: Elliott
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Zamzow
authors.forename: Michelle
authors.initials: M
authors.lastname: Combs
authors.forename: Emily
authors.initials: E
authors.lastname: Stover
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ross
authors.forename: John P
authors.initials: JP
authors.lastname: Perentesis
authors.forename: Soheil
authors.initials: S
authors.lastname: Meschinchi
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Lange
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D019014:fas Receptor / Q000235:genetics*
chemical_list: D019014:fas Receptor