title: Multilocus association of genetic variants in MLL, CREBBP, EP300, and TOP2A with childhood acute lymphoblastic leukemia in Hispanics from Texas.
abstract: BACKGROUND
  Hispanic children have both a higher incidence and a poorer outcome in acute lymphoblastic leukemia (ALL). Moreover, a higher incidence for therapy-related acute myeloid leukemia with 11q23 translocations after treatment with topoisomerase II (topo II) inhibitors has been observed in Hispanic children with ALL. We sought to determine the potential role of genetic variants within the topoisomerase IIα gene (TOP2A), within the mixed lineage leukemia gene (MLL) and two of its translocation partners, cyclin AMP response element-binding protein gene (CREBBP) and E1A binding protein gene (EP300) in the increased sensitivity of Hispanic children with ALL to topo II inhibitors.
  
  
  METHODS
  Fifty-two tagged single nucleotide polymorphisms (SNP) covering the four genes were genotyped in 241 samples (66 children with ALL and 175 age matched controls) of self-identified Hispanic origin.
  
  
  RESULTS
  Two SNPs within MLL (rs525549 and rs6589664) and three SNPs within EP300 (rs5758222, rs7286979, and rs20551) were significantly associated with ALL (P = 0.001-0.04). A significant gene-dosage effect for increasing numbers of potential high-risk genotypes (OR = 16.66; P = 2 × 10(-5)) and a major haplotype significantly associated with ALL (OR = 5.68; P = 2 × 10(-6)) were found. Replication in a sample of 137 affected White children and 239 controls showed that only rs6589664 (MLL) was significantly associated in this ethnic group.
  
  
  CONCLUSIONS
  Our findings indicate that the association between ALL and common genetic variants within MLL and EP300 is population specific.
  
  
  CONCLUSIONS
  Replication of our findings in independent Hispanic populations is warranted to elucidate the role of these variants in ALL susceptibility and define their importance in the ethnic specific differences in ALL risk.
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
authors.forename: Duangjai
authors.initials: D
authors.lastname: Piwkham
authors.forename: Jonathan A L
authors.initials: JA
authors.lastname: Gelfond
authors.forename: Budsaba
authors.initials: B
authors.lastname: Rerkamnuaychoke
authors.forename: Samart
authors.initials: S
authors.lastname: Pakakasama
authors.forename: Vivienne I
authors.initials: VI
authors.lastname: Rebel
authors.forename: Brad H
authors.initials: BH
authors.lastname: Pollock
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Anderson B
authors.initials: AB
authors.lastname: Collier
authors.forename: Gail E
authors.initials: GE
authors.lastname: Tomlinson
authors.forename: Joke
authors.initials: J
authors.lastname: Beuten
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D050882:CREB-Binding Protein / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D005260:Female; D006630:Hispanic or Latino / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human