title: MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females.
abstract: This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA. Individuals carrying heterozygous CG genotype of miR-146a rs2910164 had less risk of lung cancer than those carrying homozygous wild CC genotype (OR = 0.76, 95% CI = 0.60-0.98, P = 0.032). We found no significant association between miR-146a expression and lung cancer risk. MiR-146a expression differed in those carrying the CC genotype as compared with the CG or the GG genotype (P = 0.032 and 0.001), and the secondary structure of the C allele differed slightly from the G allele. Significantly lower levels of luciferase activity were observed when the TRAF6 3'UTR was cotransfected with miR-146a-3p carrying the rs2910164 C allele (P = 0.001). Thus, miR-146a rs2910164 polymorphism may influence susceptibility to lung cancer in Chinese nonsmoking females through targeting TRAF6.
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, PR China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, PR China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yin
authors.affiliation: School of Nursing, China Medical University, Shenyang, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, PR China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, PR China.
authors.forename: Yangwu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, PR China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, PR China.
authors.forename: Lingzi
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, PR China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, PR China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, PR China.|Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, PR China.
authors.forename: Baosen
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6; C000604754:Tifab protein, human
keywords: gene expression; genetic susceptibility; lung cancer; microRNA; single nucleotide polymorphism