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A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese

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....

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Autores principales: Wang, Bo, Zhang, Lisha, Qiu, Fuman, Fang, Wenxiang, Deng, Jieqiong, Zhou, Yifeng, Lu, Jiachun, Yang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157800/
https://www.ncbi.nlm.nih.gov/pubmed/25198518
http://dx.doi.org/10.1371/journal.pone.0106794
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author Wang, Bo
Zhang, Lisha
Qiu, Fuman
Fang, Wenxiang
Deng, Jieqiong
Zhou, Yifeng
Lu, Jiachun
Yang, Lei
author_facet Wang, Bo
Zhang, Lisha
Qiu, Fuman
Fang, Wenxiang
Deng, Jieqiong
Zhou, Yifeng
Lu, Jiachun
Yang, Lei
author_sort Wang, Bo
collection PubMed
description 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 = 0.024), with an odds ratio as 1.23(95% confidence interval  = 1.35–1.26) for the rs4713354C (CA+CC) genotypes compared to the rs4713354AA genotype. However, no significant association was observed between other SNPs and lung cancer risk. The gene-based analysis rested with these SNPs suggested the MDC1 as a susceptible gene for lung cancer (P = 0.009). 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.
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spelling pubmed-41578002014-09-09 A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese Wang, Bo Zhang, Lisha Qiu, Fuman Fang, Wenxiang Deng, Jieqiong Zhou, Yifeng Lu, Jiachun Yang, Lei PLoS One Research Article 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 = 0.024), with an odds ratio as 1.23(95% confidence interval  = 1.35–1.26) for the rs4713354C (CA+CC) genotypes compared to the rs4713354AA genotype. However, no significant association was observed between other SNPs and lung cancer risk. The gene-based analysis rested with these SNPs suggested the MDC1 as a susceptible gene for lung cancer (P = 0.009). 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. Public Library of Science 2014-09-08 /pmc/articles/PMC4157800/ /pubmed/25198518 http://dx.doi.org/10.1371/journal.pone.0106794 Text en © 2014 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Bo
Zhang, Lisha
Qiu, Fuman
Fang, Wenxiang
Deng, Jieqiong
Zhou, Yifeng
Lu, Jiachun
Yang, Lei
A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese
title A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese
title_full A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese
title_fullStr A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese
title_full_unstemmed A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese
title_short A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese
title_sort newfound association between mdc1 functional polymorphism and lung cancer risk in chinese
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157800/
https://www.ncbi.nlm.nih.gov/pubmed/25198518
http://dx.doi.org/10.1371/journal.pone.0106794
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