title: Polymorphism in IKZF1 gene affects age at onset of childhood acute lymphoblastic leukemia.
abstract: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, characterized by a peak of incidence between 2 and 5 years. Since recently conducted genome-wide association (GWA) studies revealed that the common low-penetrance susceptibility allele at 7p12.2 (IKZF1 gene) confers an increased risk of pediatric ALL, we investigated whether the risk allele at rs4132601 also coexists with well-established prognostic factors, among 508 Polish pediatric patients with newly diagnosed ALL. Additionally, to verify whether the risk allele is favored by somatic tumor evolution, we examined the incidence of IKZF1 deletions in leukemic clones derived from 153 previously genotyped cases of pediatric ALL. Results of the analysis provide statistically significant support for an association between the rs4132601 polymorphic site and age at diagnosis of childhood ALL (p = 0.04). No association between allele variant and occurrence of IKZF1 deletions was found. These data provide further evidence of a biological role of gene variants in the development of ALL.
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz , Poland.
authors.forename: Patryk
authors.initials: P
authors.lastname: Górniak
authors.forename: Agata
authors.initials: A
authors.lastname: Pastorczak
authors.forename: Beata
authors.initials: B
authors.lastname: Zalewska-Szewczyk
authors.forename: Monika
authors.initials: M
authors.lastname: Lejman
authors.forename: Joanna
authors.initials: J
authors.lastname: Trelińska
authors.forename: Marta
authors.initials: M
authors.lastname: Chmielewska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sokół-Jeżewska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.forename: Michał
authors.initials: M
authors.lastname: Matysiak
authors.forename: Bernarda
authors.initials: B
authors.lastname: Kazanowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D017668:Age of Onset; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D016130:Immunophenotyping; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis
chemical_list: C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor
keywords: Acute lymphoblstic leukemia; IKZF1; polymorphism