title: Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics.
abstract: Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case-control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10(-9) to 0.004) and NHWs (p values of 2.2 × 10(-6) to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53-1.99 and 1.37-1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21-3.22 and 1.67-2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10(-5)), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors.
authors.affiliation: Division of Epidemiology, School of Public Health, University of California, 1995 University Ave, Ste 460, Berkeley, CA, 94704, USA, anandc@berkeley.edu.
authors.forename: Anand P
authors.initials: AP
authors.lastname: Chokkalingam
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hansen
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Month
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Buffler
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002140:California; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C503805:ARID5B protein, human; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C070790:CEBPE protein, human