title: ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome.
  
  
  METHODS
  We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials.
  
  
  RESULTS
  Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10(-20) in whites; P = 1 × 10(-6) in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10(-8)). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics.
  
  
  CONCLUSIONS
  ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.
authors.affiliation: St. Jude Children’s Research Hospital, Memphis, TN 38105-3678, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fan
authors.forename: Wenjian
authors.initials: W
authors.lastname: Yang
authors.forename: Geoff
authors.initials: G
authors.lastname: Neale
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Frederico
authors.initials: F
authors.lastname: Antillon
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Paul L
authors.initials: PL
authors.lastname: Martin
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Mignon
authors.initials: M
authors.lastname: Loh
authors.forename: William E
authors.initials: WE
authors.lastname: Evans
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.forename: Jun J
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D016022:Case-Control Studies; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D054624:Health Status Disparities; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015994:Incidence; D007198:Indians, North American / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors