title: Genetic variants in microRNA-146a (C>G) and microRNA-1269b (G>C) are associated with the decreased risk of oral premalignant lesions, oral cancer, and pharyngeal cancer.
abstract: OBJECTIVE
  To investigate the relationships between two single-nucleotide polymorphisms at miR-146a C>G (rs2910164) and miR-1269b G>C (rs7210937) and the risk of developing oral premalignant lesions (OPLs), oral squamous cell carcinoma (OSCC), pharyngeal SCC (PSCC), and oral and pharyngeal SCC (OPSCC).
  
  
  METHODS
  Genotyping of miR-146a C>G and miR-1269b G>C was performed in two case-control studies using the TaqMan assay. A total of 197 healthy control subjects, 241 OPLs patients, and 188 OPSCC patients who habitually chewed betel quid (BQ) were recruited into one case-control study. Additionally, 668 cancer-free control subjects and 658 OPSCC patients were recruited into the other case-control study.
  
  
  RESULTS
  The G/G genotype at miR-146a C>G was associated with the decreased risk of OSCC [adjusted odds ratio (AOR)=0.66, P=0.040], PSCC (AOR=0.42, P=0.013), and OPSCC (AOR=0.63, P=0.020). Additionally, the C allelic type and C/C genotype at miR-1269b G>C decreased the risk of BQ-related oral leukoplakia (C vs. G: AOR=0.68, P=0.012;C/C vs. G/G: AOR=0.43, P=0.009), BQ-related OPLs (C vs. G: AOR=0.69, P=0.008;C/C vs. G/G: AOR=0.44, P=0.005), and BQ-related OPSCC (C vs. G: AOR=0.65, P=0.003;C/C vs. G/G: AOR=0.47, P=0.011). In OPSCC patients, the G/G genotype of miR-146a was correlated with well-differentiated cells (P=0.041), and the G/C and C/C genotypes of miR-1269b were correlated with the absence of lymph node involvement (P=0.031), especially in OSCC patients (P=0.038 and P=0.007, respectively).
  
  
  CONCLUSIONS
  The genetic variants of miR-146a and miR-1269b are biomarkers against the development of OPLs and OPSCC.
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan; Department of Orthopedics, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Yu-Kai
authors.initials: YK
authors.lastname: Tseng
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Chi
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Yang
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Sin-Jhih
authors.initials: SJ
authors.lastname: Huang
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Nursing, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Huei-Han
authors.initials: HH
authors.lastname: Liou
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan. Electronic address: kwtsai@vghks.gov.tw.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. Electronic address: lpger@vghks.gov.tw.
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
mesh_terms: D000328:Adult; D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D010610:Pharyngeal Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics*; D012306:Risk
chemical_list: C000600169:MIRN1269 microRNA, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs
keywords: Oral cancer; Pharyngeal cancer; Polymorphisms; Risk; miR-1269b; miR-146a