title: Association of genetic variation in IKZF1, ARID5B, CDKN2A, and CEBPE with the risk of acute lymphoblastic leukemia in Tunisian children and their contribution to racial differences in leukemia incidence.
abstract: Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.3), and CEBPE (14q11.2) are strongly associated to the risk of developing pediatric ALL. These studies have been conducted in European and Thai populations, and it is unclear whether these observations generalize to other populations with a lower incidence of pediatric ALL. In order to explore the impact of these variants on pediatric ALL risk in the Tunisian population, we genotyped 58 cases of pediatric ALL and 150 controls for SNPs rs4132601 (7p12.2), rs7089424 (10q21.2), rs3731217 (9p21.3), and rs2239633 (14q11.2). Our results, which are consistent with findings in European populations, show that 3 SNPs, i.e., rs4132601 (P = .00116, odds ratio [OR] = 2.78, 95% confidence interval [CI] = [1.42, 5.87]), rs7089424 (P = .0022, OR = 0.49, 95% CI = [0.31, 0.79]), and rs2239633 (P = .0010, OR = 0.47, 95% CI = [0.29, 0.75]) are significantly associated with a higher risk of developing pediatric ALL (P < .05). Furthermore, we show differences in allele frequencies in SNPs between Tunisian and Caucasian and/or Thai populations (e.g., CEBPE, rs2239633; population attributable risk [PAR] ∼15-fold the PAR of Thai population). These differences, combined with differences in linkage disequilibrium structure between populations and differences in size between populations, may contribute to racial differences in pediatric ALL incidence.
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Hanene
authors.initials: H
authors.lastname: Gharbi
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Islem
authors.initials: I
authors.lastname: Ben Hassine
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Ismail
authors.initials: I
authors.lastname: Soltani
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Safra
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Slah
authors.initials: S
authors.lastname: Ouerhani
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Hind
authors.initials: H
authors.lastname: Bel Haj Othmen
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Mouheb
authors.initials: M
authors.lastname: Teber
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Farah
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Hassiba
authors.initials: H
authors.lastname: Amouri
authors.affiliation: b Laboratory of Hematology Bechir Hamza Hospital , Tunis , Tunisia.
authors.forename: Nourel Houda
authors.initials: NH
authors.lastname: Toumi
authors.affiliation: c Hematology Service Hospital Aziza Othmana , Tunis , Tunisia.
authors.forename: Salima
authors.initials: S
authors.lastname: Abdennebi
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
authors.affiliation: a Laboratory of Molecular and Cellular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.
authors.forename: Samia
authors.initials: S
authors.lastname: Menif
mesh_terms: D000293:Adolescent; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C503805:ARID5B protein, human; D022762:CCAAT-Enhancer-Binding Proteins; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; C070790:CEBPE protein, human; D051740:Ikaros Transcription Factor
keywords: ALL; ARID5B; CDKN2A; CEBPE; IKZF1; racial differences