title: A Newfound association between MDC1 functional polymorphism and lung cancer risk in Chinese.
abstract: Mediator of DNA damage checkpoint protein 1 (MDC1) plays an early and core role in Double-Strand Break Repair (DDR) and ataxia telangiectasia-mutated (ATM) mediated response to DNA double-strand breaks (DSBs), and thus involves the pathogenesis of several DNA damage-related diseases such as cancer. We hypothesized that the single nucleotide polymorphisms (SNPs) of MDC1 which have potencies on affecting MDC1 expression or function were associated with risk of lung cancer. In a two-stage case-control study, we tested the association between 5 putatively functional SNPs of MDC1 and lung cancer risk in a southern Chinese population, and validated the promising association in an eastern Chinese population. We found the SNP rs4713354A>C that is located in the 5′-untranslated region of MDC1 was significantly associated with lung cancer risk in both populations (P = 0.001), with an odds ratio as 1.33(95% confidence interval = 1.14–1.55) for the rs4713354C (CA+CC) genotypes compared to the rs4713354AA genotype. The correct sixth sentence is: The gene-based analysis rested with these SNPs suggested the MDC1 as a susceptible gene for lung cancer (P = 0.057) [corrected]. Moreover, by querying the gene expression database, we further found that the rs4713354C genotypes confer a significantly lower mRNA expression of MDC1 than the rs4713354AA genotype in 260 cases of lymphoblastoid cells (P = 0.002). Our data suggested that the SNP rs4713354A>C of MDC1 may be a functional genetic biomarker for susceptibility to lung cancer in Chinese.
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Deng
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002681:China; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators