FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.
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.
Mehta
Parinda A
PA
Division of Hematology/Oncology, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio 45229, USA. parinda.mehta@cchmc.org
Gerbing
Robert B
RB
Alonzo
Todd A
TA
Elliott
James S
JS
Zamzow
Tiffany A
TA
Combs
Michelle
M
Stover
Emily
E
Ross
Julie A
JA
Perentesis
John P
JP
Meschinchi
Soheil
S
Lange
Beverly J
BJ
Davies
Stella M
SM
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*
D019014:fas Receptor