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Genetic Variants in the p14ARF/MDM2/TP53 Pathway Are Associated with the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated with Radical Resection

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  • Jing Li
  • Yang Tang
  • Liu Huang
  • Qianqian Yu
  • Guangyuan Hu
  • Xianglin Yuan

Abstract

The p14ARF/MDM2/ TP53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in the p14ARF/MDM2/TP53 pathway and prognosis in ESCC patients with radical resection. 124 ESCC patients with radical resection were included in this retrospective study and genotyped using the MassArray method. According to multivariate Cox hazard analysis and multiple testing, the TC/CC genotype of p14ARF rs3814960 was shown to be strongly related to a decreased overall survival (OS) (HR = 2.77, 95% CI: 1.33–5.75, P = 0.006, Pc = 0.030) and disease-free survival (DFS) (HR = 2.45, 95% CI: 1.30–4.61, P = 0.005, Pc = 0.025). Moreover, patients with the DEL/A +AA genotype of MDM2 rs34886328 had a notably increased OS (HR = 0.27, 95% CI: 0.13–0.56, P = 4.7×10−4, Pc = 0.003) and DFS (HR = 0.22, 95% CI: 0.11–0.43, P = 1.1×10−5, Pc = 6.6×10−5). We also found that these two SNPs had a cumulative effect on the prognosis of ESCC, with the OS (P

Suggested Citation

  • Jing Li & Yang Tang & Liu Huang & Qianqian Yu & Guangyuan Hu & Xianglin Yuan, 2016. "Genetic Variants in the p14ARF/MDM2/TP53 Pathway Are Associated with the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated with Radical Resection," PLOS ONE, Public Library of Science, vol. 11(7), pages 1-11, July.
    • Handle: RePEc:plo:pone00:0158613
    DOI: 10.1371/journal.pone.0158613
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    References listed on IDEAS

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    1. Jun Zhang & Zhiwei Xu & Lingxiang Yu & Meilan Chen & Ke Li, 2014. "Assessment of the Potential Diagnostic Value of Serum p53 Antibody for Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-9, June.
    2. Ygal Haupt & Ruth Maya & Anat Kazaz & Moshe Oren, 1997. "Mdm2 promotes the rapid degradation of p53," Nature, Nature, vol. 387(6630), pages 296-299, May.
    3. Michael H. G. Kubbutat & Stephen N. Jones & Karen H. Vousden, 1997. "Regulation of p53 stability by Mdm2," Nature, Nature, vol. 387(6630), pages 299-303, May.
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