title: Polymorphisms in miRNA processing genes and their role in osteosarcoma risk.
abstract: BACKGROUND
  The possible associations between genetic variants and osteosarcoma risk have been analyzed without conclusive results. Those studies were focused mainly on genes of biologically plausible pathways. However, recently, another pathway has acquired relevance in cellular transformation and tumorigenesis, the microRNA (miRNA) processing pathway. Dysregulation of the expression levels of genes in this pathway has been described in cancer. Consequently, single nucleotide polymorphisms (SNPs) in genes that codify for proteins involved in the miRNA processing pathway may affect miRNAs, and therefore their target genes, which might be associated with cancer development and progression. The aim of this study was to evaluate whether SNPs in miRNA processing genes confer predisposition to osteosarcoma.
  
  
  METHODS
  We analyzed 72 SNPs in 21 miRNA processing genes in a total of 99 osteosarcoma patients and 387 controls.
  
  
  RESULTS
  A total of three SNPs were associated with osteosarcoma susceptibility. Interestingly, these SNPs were located in miRNA processing genes (CNOT1, CNOT4 and SND1) which are part of the RISC complex. Among them, the association of rs11866002 in CNOT1 was nearly significant after Bonferroni correction.
  
  
  CONCLUSIONS
  This study suggests that SNPs in RISC complex genes may be involved in osteosarcoma susceptibility, especially rs11866002 in CNOT1.
authors: Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors: Nerea
authors: N
authors: Bilbao-Aldaiturriaga
authors: Angela
authors: A
authors: Gutierrez-Camino
authors: Idoia
authors: I
authors: Martin-Guerrero
authors: Maria
authors: M
authors: Pombar-Gomez
authors: Marta
authors: M
authors: Zalacain-Diez
authors: Ana
authors: A
authors: Patiño-Garcia
authors: Elixabet
authors: E
authors: Lopez-Lopez
authors: Africa
authors: A
authors: Garcia-Orad
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004720:Endonucleases; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C528690:CNOT1 protein, human; C501331:CNOT4 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D014157:Transcription Factors; D004720:Endonucleases; C095221:SND1 protein, human
keywords: genetic susceptibility; microRNA processing pathway; osteosarcoma