title: The association between miR-499a polymorphism and oral squamous cell carcinoma progression.
abstract: OBJECTIVE
  To investigate the association of miR-499a genetic polymorphism with the risk of oral leukoplakia, oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC), and clinicopathological outcomes of OSCC.
  
  
  METHODS
  The genotyping of miR-499a T>C (rs3746444) using TagMan assay was conducted in two case-control studies of 1549 subjects. miR-499a-5p and miR-499a-3p were assayed using stem-loop RT-PCR for 63 paired OSCC and adjacent normal tissues.
  
  
  RESULTS
  T/C+C/C genotypes [adjusted odds ratio (AOR) 1.84, P = 0.032] and C allelic type (AOR 1.91, P = 0.007) at miR-499a T>C were associated with an increased risk of BQ-related OSF as compared to those with T/T genotype or T allelic type, respectively. Conversely, T/C+C/C genotypes and C allelic type decreased the risk of OSCC, especially for non-BQ-related OSCC (for genotype: AOR 0.49, P = 0.010; for allelic type: AOR 0.50, P = 0.007). Additionally, downregulation of miR-499a-5p was found in OSCC tissues (P = 0.001) and correlated with the TT genotype (P = 0.001).
  
  
  CONCLUSIONS
  The T/C+C/C genotypes of MiR-499a may contribute to an increased risk of BQ-related OSF, but a decreased risk of OSCC. miR-499a T>C influences the expression levels of miR-499a-5p during the tumorigenesis of OSCC.
authors.affiliation: Department of Otorhinolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Nursing, Yuh-Ing Junior College of Health Care and Management, Kaohsiung, Taiwan.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Hou
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.forename: H-C
authors.initials: HC
authors.lastname: Chen
authors.forename: C-M
authors.initials: CM
authors.lastname: Yang
authors.forename: S-J
authors.initials: SJ
authors.lastname: Huang
authors.forename: H-H
authors.initials: HH
authors.lastname: Liou
authors.forename: C-C
authors.initials: CC
authors.lastname: Chi
authors.forename: K-W
authors.initials: KW
authors.lastname: Tsai
authors.forename: L-P
authors.initials: LP
authors.lastname: Ger
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009914:Oral Submucous Fibrosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C548683:MIRN499 microRNA, human; D035683:MicroRNAs
keywords: miR-499a; microRNA; oral cancer; oral submucous fibrosis; polymorphism; progression