title: Noncoding RNA-related polymorphisms in pediatric acute lymphoblastic leukemia susceptibility.
abstract: BACKGROUND
  Evidence for an inherited genetic risk for pediatric acute lymphoblastic leukemia has been provided in several studies. Most of them focused on coding regions. However, those regions represent only 1.5% of the entire genome. In acute lymphoblastic leukemia (ALL), it has been suggested that the expression of microRNAs (miRNAs) is dysregulated, which suggests that they may have a role in ALL risk. Changes in miRNA function may occur through single-nucleotide polymorphisms (SNPs). Therefore, the aim of this study was to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA-processing genes, contribute to a predisposition for childhood ALL.
  
  
  METHODS
  In this study, we analyzed 118 SNPs in pre-miRNAs and miRNA-processing genes in 213 B-cell ALL patients and 387 controls.
  
  
  RESULTS
  We found 11 SNPs significantly associated with ALL susceptibility. These included three SNPs present in miRNA genes (miR-612, miR-499, and miR-449b) and eight SNPs present in six miRNA biogenesis pathway genes (TNRC6B, DROSHA, DGCR8, EIF2C1, CNOT1, and CNOT6). Among the 118 SNPs analyzed, rs12803915 in mir-612 and rs3746444 in mir-499 exhibited a more significant association, with a P value <0.01.
  
  
  CONCLUSIONS
  The results of this study indicate that SNP rs12803915 located in pre-mir-612, and SNP rs3746444 located in pre-mir-499, may represent novel markers of B-cell ALL susceptibility.
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Gutierrez-Camino
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Elixabet
authors.initials: E
authors.lastname: Lopez-Lopez
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Idoia
authors.initials: I
authors.lastname: Martin-Guerrero
authors.affiliation: Department of Hematology and Hemotherapy, University Hospital Cruces, Bilbao, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Piñan
authors.affiliation: Service of Pediatric Oncohematology, University Hospital La Paz, Madrid, Spain.
authors.forename: Purificacion
authors.initials: P
authors.lastname: Garcia-Miguel
authors.affiliation: Service of Pediatric Oncology and Hematology, University Hospital Vall d' Hebron, VHIR, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Sanchez-Toledo
authors.affiliation: Unit of Pediatric Oncohematology, University Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Carbone Bañeres
authors.affiliation: Unit of Pediatric Oncohematology, University Hospital Donostia, San Sebastian, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Uriz
authors.affiliation: Unit of Pediatric Hematology/Oncology, University Hospital Cruces, Bilbao, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Navajas
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Africa
authors.initials: A
authors.lastname: Garcia-Orad
mesh_terms: D002648:Child; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: C548683:MIRN499 microRNA, human; C582274:MIRN612 microRNA, human; D035683:MicroRNAs; D022661:RNA, Untranslated