title: Association of genetic variation in IKZF1, ARID5B, and CEBPE and surrogates for early-life infections with the risk of acute lymphoblastic leukemia in Hispanic children.
abstract: BACKGROUND
  Genome-wide association studies focusing on European-ancestry populations have identified ALL risk loci on IKZF1, ARID5B, and CEBPE. To capture the impacts of these genes on ALL risk in the California Hispanic population, we comprehensively assessed the variation within the genes and further assessed the joint effects between the genetic variation and surrogates for early-life infections (the presence of older siblings, daycare attendance, and ear infections).
  
  
  METHODS
  Genotypic data for 323 Hispanic ALL cases and 454 controls from the California Childhood Leukemia Study were generated using Illumina OmniExpress v1 platform. Logistic regression assuming a log-additive model estimated odds ratios (OR) associated with each SNP, adjusted for age, sex, and the first five principal components. In addition, we examined potential interactions between six ALL risk alleles and surrogates for early-life infections using logistic regression models that included an interaction term.
  
  
  RESULTS
  Significant associations between genotypes at IKZF1, ARID5B, and CEBPE and ALL risk were identified: rs7780012, OR 0.50, 95% confidence interval (CI) 0.35-0.71 (p = 0.004); rs7089424, OR 2.12, 95% CI 1.70-2.65 (p = 1.16 × 10(-9)); rs4982731, OR 1.69, 95% CI 1.37-2.08 (p = 2.35 × 10(-6)), respectively. Evidence for multiplicative interactions between genetic variants and surrogates for early-life infections with ALL risk was not observed.
  
  
  CONCLUSIONS
  Consistent with findings in non-Hispanic White population, our study showed that variants within IKZF1, ARID5B, and CEBPE were associated with increased ALL risk, and the effects for ARID5B and CEBPE were most prominent in the high-hyperdiploid ALL subtype in the California Hispanic population. Results implicate the ARID5B, CEBPE, and IKZF1 genes in the pathogenesis of childhood ALL.
authors.affiliation: School of Public Health, University of California, Berkeley, Berkeley, CA, 94720, USA, lingi.hsu732@gmail.com.
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.forename: Anand P
authors.initials: AP
authors.lastname: Chokkalingam
authors.forename: Farren B S
authors.initials: FB
authors.lastname: Briggs
authors.forename: Kyle
authors.initials: K
authors.lastname: Walsh
authors.forename: Vonda
authors.initials: V
authors.lastname: Crouse
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fu
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Buffler
mesh_terms: D000483:Alleles; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002140:California; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C503805:ARID5B protein, human; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; C070790:CEBPE protein, human; D051740:Ikaros Transcription Factor