title: ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia.
abstract: BACKGROUND
  Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as MLL rearrangements (MLL-r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of IKZF1, ARID5B, and CEBPE could be related to the onset of EAL cases (<24 months-old at diagnosis).
  
  
  METHODS
  The SNPs (IKZF1 rs11978267, ARID5B rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI).
  
  
  RESULTS
  Children with the IKZF1 SNP had an increased risk of developing MLL-germline ALL in white children. The heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the risk for MLL-germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in ARID5B rs10821936 increased the risk for MLL-r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL-MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that CEBPE rs2239633 confers increased genetic susceptibility to EAL.
  
  
  CONCLUSIONS
  IKZF1 and CEBPE variants seem to play a minor role in genetic susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3. This result shows that genetic susceptibility could be associated with the differences regarding MLL breakpoints and partner genes.
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.forename: Thayana Conceição
authors.initials: TC
authors.lastname: Barbosa
authors.forename: Bruno Almeida
authors.initials: BA
authors.lastname: Lopes
authors.forename: Caroline Barbieri
authors.initials: CB
authors.lastname: Blunck
authors.forename: Alessandra
authors.initials: A
authors.lastname: Faro
authors.forename: Camilla
authors.initials: C
authors.lastname: Andrade
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro/RJ 20231-050, Brasil. mpombo@inca.gov.br.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
mesh_terms: D000367:Age Factors; D001938:Brazil; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D016017:Odds Ratio; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein