title: A common polymorphism in pre-microRNA-146a is associated with lung cancer risk in a Korean population.
abstract: BACKGROUND
  MicroRNAs (miRs) play important roles in the development and progression of human cancers. MiR-146a down-regulates epidermal growth factor receptor and the nuclear factor-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that play important roles in lung carcinogenesis. This study was conducted to evaluate the association between rs2910164C>G, a functional polymorphism in the pre-miR-146a, and lung cancer risk.
  
  
  METHODS
  The rs2910164C>G genotypes were determined in 1094 patients with lung cancer and 1100 healthy controls who were frequency matched for age and gender.
  
  
  RESULTS
  The rs2910164 CG or GG genotype was associated with a significantly decreased risk for lung cancer compared to that of the CC genotype (adjusted odds ratio=0.80, 95% confidence interval=0.66-0.96, P=0.02). When subjects were stratified according to smoking exposure (never, light and heavy smokers), the effect of the rs2910164C>G genotype on lung cancer risk was significant only in never smokers (adjusted odds ratio=0.66, 95% confidence interval=0.45-0.96, P=0.03, under a dominant model for the C allele) and decreased as smoking exposure level increased (Ptrend<0.001). In line with this result, the level of miR-146a expression in the tumor tissues was significantly higher in the GG genotype than in the CC or CG genotype only in never-smokers (P=0.02).
  
  
  CONCLUSIONS
  These findings suggest that the rs2910164C>G in pre-miR-146a may contribute to genetic susceptibility to lung cancer, and that miR-146a might be involved in lung cancer development.
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu 700-422, South Korea; Lung Cancer Center, Kyungpook National University Medical Center, 807, Hoguk-ro, Buk-gu, Daegu 702-210, South Korea. Electronic address: jeonh@knu.ac.kr.
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Jang
authors.forename: Yi-Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs
keywords: ACs; BRCA1; CIs; EGFR; HWE; Hardy–Weinberg equilibrium; IRAK1; Lung cancer; MicroRNA; NF-κB; P(H); P-values of the homogeneity test; RT-PCR; Risk factor; SCCs; SCLC; SNPs; aORs; adenocarcinomas; adjusted odds ratios; breast cancer 1, early onset; confidence intervals; epidermal growth factor receptor; interleukin-1 receptor-associated kinase 1; miR-146a; miRs; microRNAs; nuclear factor-κB; reverse transcription-polymerase chain reaction; single nucleotide polymorphisms; small cell lung cancers; squamous cell carcinomas