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FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.

Mehta, Parinda A and Gerbing, Robert B and Alonzo, Todd A and Elliott, James S and Zamzow, Tiffany A and Combs, Michelle and Stover, Emily and Ross, Julie A and Perentesis, John P and Meschinchi, Soheil and Lange, Beverly J and Davies, Stella M (2008) FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report. Clinical cancer research : an official journal of the American Association for Cancer Research, 14 (23). pp. 7896-7899. ISSN 1078-0432

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PURPOSE: 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. EXPERIMENTAL DESIGN: 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.

Item Type: Article or Abstract
Additional Information: This article is freely available at the journal site and in PubMed Central.
DOI: 10.1158/1078-0432.CCR-08-0418
PubMed ID: 19047119
PMCID: PMC2787450
Keywords or MeSH Headings: Adolescent; Adult; Antigens, CD95/genetics; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Drug Resistance, Neoplasm/genetics; Genotype; Humans; Infant; Infant, Newborn; Kaplan-Meiers Estimate; Leukemia, Myeloid, Acute/drug therapy/genetics/mortality; Pilot Projects; Polymorphism, Single Nucleotide; Promoter Regions, Genetic/genetics; Randomized Controlled Trials as Topic; Treatment Outcome;
Depositing User: Library Staff
Date Deposited: 22 Feb 2010 19:55
Last Modified: 14 Feb 2012 14:42

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