XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report.
Genetic polymorphisms result in interindividual variation in DNA repair capacity and may, in part, account for susceptibility of a cell to genotoxic agents and to malignancy. Polymorphisms in XPD, a member of the nucleotide excision repair pathway, have been associated with development of treatment-related acute myeloid leukemia (AML) and with poor outcome of AML in elderly patients. We hypothesized that XPD Lys751Gln polymorphism may play a role in causation of AML in children and, as shown in adults, may affect the outcome of childhood AML therapy. Genotyping of 456 children treated for de novo AML was performed at XPD exon 23. Genotype frequencies in patients were compared with healthy control subject frequencies, and patient outcomes were analyzed according to genotype. Gene frequencies in AML patients and healthy controls were similar. There were no significant differences in overall survival (P = .82), event-free survival (P = .78), treatment-related mortality (P = .43), or relapse rate (RR) (P = .92) between patients with XPD751AA versus 751AC versus 751CC genotypes, in contrast to reports in adult AML. These data, representing the only data in pediatric AML, suggest that XPD genotype does not affect the etiology or outcome of childhood AML.
Mehta
Parinda A
PA
Cincinnati Children's Hospital and Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA. Parinda.Mehta@cchmc.org
Alonzo
Todd A
TA
Gerbing
Robert B
RB
Elliott
James S
JS
Wilke
Tiffany A
TA
Kennedy
Rebekah J
RJ
Ross
Julie A
JA
Perentesis
John P
JP
Lange
Beverly J
BJ
Davies
Stella M
SM
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human