title: The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased risk of lung cancer in Chinese populations: case-control and a meta-analysis.
abstract: NBS1 plays pivotal roles in maintaining genomic stability and cancer development. The exon variant rs1805794G>C (p.Glu185Gln) of NBS1 has been frequently studied in several association studies. However, the results were conflicting. Also, the function of this variant has never been well studied. In the current study, we performed a two centers case-control study and function assays to investigate the effect of the variant rs1805794G>C on lung cancer risk in Chinese, and a meta-analysis to summarize the data on the association between rs1805794G>C and cancer risk. We found that compared with the rs1805794GG genotype, the C genotypes (CG/CC) conferred a significantly increased risk of lung cancer in Chinese (OR=1.40, 95% CI=1.21-1.62) and interacted with medical ionizing radiation exposure on increasing cancer risk (Pinteraction=0.015). The lymphocyte cells from the C genotype individuals developed more chromatid breaks than those from the GG genotype carriers after the X-ray radiation (P=0.036). Moreover, the rs1805794C allele encoding p.185Gln attenuated NBS1's ability to repair DNA damage as the cell lines transfected with NBS1 cDNA expression vector carrying rs1805794C allele had significantly higher DNA breaks than those transfected with NBS1 cDNA expression vector carrying rs1805794G allele (P<0.05). The meta-analysis further confirmed the association between the variant rs1805794G>C and lung cancer risk, that compared with the GG genotype, the carriers of C genotypes had a 1.30-fold risk of cancer (95% CI=1.14-1.49, P=8.49×10(-5)). These findings suggest that the rs1805794G>C of NBS1 may be a functional genetic biomarker for lung cancer.
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Cardio-thoracic Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182, China. Electronic address: jcLu@gzhmu.edu.cn.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D005973:Glutamine; D018698:Glutamic Acid
keywords: Lung cancer; NBS1; Polymorphism