title: A functional polymorphism at microRNA-629-binding site in the 3'-untranslated region of NBS1 gene confers an increased risk of lung cancer in Southern and Eastern Chinese population.
abstract: The genetic variations in NBS1 gene have been reported to be associated with cancer risk. The polymorphisms in 3'-untranslated region (3'-UTR) of NBS1 might affect gene's function and thus contribute to cancer susceptibility. We hypothesized that these polymorphisms of NBS1 are associated with the lung cancer risk. In two independent case-control studies conducted in Southern and Eastern Chinese, we genotyped three tagSNPs (rs14448, rs13312986 and rs2735383) in Southern Chinese and then validated the discovered association in Eastern Chinese. No significant association was observed for rs13312986 and rs14448; we only found that the rs2735383CC genotype had a significantly increased risk of lung cancer under a recessive genetic model in the total 1559 cases versus 1679 controls (odds ratio = 1.40, 95% confidence interval = 1.18-1.66, P = 0.0001) when compared with GG or GC genotypes; the rs2735383CC genotype carriers had lower messenger RNA and protein expression levels in tumor tissues than those of other genotypes as quantitative polymerase chain reaction and western blot shown. Luciferase assay revealed that the rs2735383C allele had a lower transcription activity than G allele, and the hsa-miR-629 but not hsa-miR-499-5P had effect on modulation of NBS1 gene in vitro. We further observed that the X-ray radiation induced more chromatid breaks in lymphocyte cells from the carriers of rs2735383CC homozygote than those from the subjects with other genotypes (P = 0.0008). Our data suggested that the rs2735383G>C variation contributes to an increased risk of lung cancer by diminishing gene's expression through binding of microRNA-629 to the polymorphic site in the 3'-UTR of NBS1 gene.
authors: The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, People's Republic of China.
authors: Lei
authors: L
authors: Yang
authors: Yinyan
authors: Y
authors: Li
authors: Mei
authors: M
authors: Cheng
authors: Dongsheng
authors: D
authors: Huang
authors: Jian
authors: J
authors: Zheng
authors: Bin
authors: B
authors: Liu
authors: Xiaoxuan
authors: X
authors: Ling
authors: Qingchu
authors: Q
authors: Li
authors: Xin
authors: X
authors: Zhang
authors: Weidong
authors: W
authors: Ji
authors: Yifeng
authors: Y
authors: Zhou
authors: Jiachun
authors: J
authors: Lu
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001665:Binding Sites; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D019457:Chromosome Breakage; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C569688:MIRN629 microRNA, human; D035683:MicroRNAs; C112156:NBN protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger