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

Author

Listed:
  • Bo Wang
  • Lisha Zhang
  • Fuman Qiu
  • Wenxiang Fang
  • Jieqiong Deng
  • Yifeng Zhou
  • Jiachun Lu
  • Lei Yang

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 = 0.024), 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.

Suggested Citation

  • Bo Wang & Lisha Zhang & Fuman Qiu & Wenxiang Fang & Jieqiong Deng & Yifeng Zhou & Jiachun Lu & Lei Yang, 2014. "A Newfound Association between MDC1 Functional Polymorphism and Lung Cancer Risk in Chinese," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-7, September.
    • Handle: RePEc:plo:pone00:0106794
    DOI: 10.1371/journal.pone.0106794
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    References listed on IDEAS

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    1. Grant S. Stewart & Bin Wang & Colin R. Bignell & A. Malcolm R. Taylor & Stephen J. Elledge, 2003. "MDC1 is a mediator of the mammalian DNA damage checkpoint," Nature, Nature, vol. 421(6926), pages 961-966, February.
    2. Michal Goldberg & Manuel Stucki & Jacob Falck & Damien D'Amours & Dinah Rahman & Darryl Pappin & Jiri Bartek & Stephen P. Jackson, 2003. "MDC1 is required for the intra-S-phase DNA damage checkpoint," Nature, Nature, vol. 421(6926), pages 952-956, February.
    3. Zhenkun Lou & Katherine Minter-Dykhouse & Xianglin Wu & Junjie Chen, 2003. "MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways," Nature, Nature, vol. 421(6926), pages 957-961, February.
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