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Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx.

Publication ,  Journal Article
Lu, Z; Sturgis, EM; Zhu, L; Zhang, H; Tao, Y; Wei, P; Wei, Q; Li, G
Published in: Mol Carcinog
March 2018

Given the crucial role of Mouse double minute 4 (MDM4) oncoprotein in p53 pathway, single nucleotide polymorphisms (SNPs) could serve as such biomarkers for prediction of SCCOP recurrence. Thus, we investigated associations between three tagging putatively functional variants of MDM4, two in the 3' untranslated region of 3' UTR [rs11801299 (NC_000001.10:g.204529084G>A) and rs10900598(NC_000001.10:g.204525568G>T)] and one in intron 1 [rs1380576(NC_000001.10:g.204488278G>C)], and recurrence risk of SCCOP in 1,008 incident patients. A log-rank test and multivariable Cox models were used to assess associations. Patients with MDM4-rs10900598 GT/TT had a worse disease-free survival (DFS) compared with corresponding GG genotype, while those with rs11801299 AG/AA genotypes had a lower recurrence risk than the cases with rs11801299 GG genotype (both log-rank, P < 0.001). Multivariable analysis showed that significantly different recurrence risk were found among patients with MDM4-rs10900598 GT/TT and rs11801299 AG/AA variant genotypes (HR, 2.0, 95% CI, 1.4-2.9 and HR, 0.4, 95% CI, 0.3-0.6, respectively) compared with their corresponding common homozygous genotypes. Furthermore, after combining the risk genotypes of the three SNPs, patients among low-risk group had a significantly lower risk of SCCOP recurrence than those in high-risk group (HR, 0.2, 95% CI, 0.1-0.3). The risk for both individual SNPs or combined risk genotypes was restricted to HPV-positive SCCOP patients. Our findings suggest that the MDM4 polymorphisms may, individually or in combination, confer an independent risk of SCCOP recurrence, particularly in HPV-positive SCCOP patients. However, larger studies are needed to validate our findings.

Duke Scholars

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

March 2018

Volume

57

Issue

3

Start / End Page

361 / 369

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins
  • Polymorphism, Single Nucleotide
  • Papillomavirus Infections
  • Oropharyngeal Neoplasms
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lu, Z., Sturgis, E. M., Zhu, L., Zhang, H., Tao, Y., Wei, P., … Li, G. (2018). Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog, 57(3), 361–369. https://doi.org/10.1002/mc.22760
Lu, Zhongming, Erich M. Sturgis, Lijun Zhu, Hua Zhang, Ye Tao, Peng Wei, Qingyi Wei, and Guojun Li. “Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx.Mol Carcinog 57, no. 3 (March 2018): 361–69. https://doi.org/10.1002/mc.22760.
Lu Z, Sturgis EM, Zhu L, Zhang H, Tao Y, Wei P, et al. Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog. 2018 Mar;57(3):361–9.
Lu, Zhongming, et al. “Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx.Mol Carcinog, vol. 57, no. 3, Mar. 2018, pp. 361–69. Pubmed, doi:10.1002/mc.22760.
Lu Z, Sturgis EM, Zhu L, Zhang H, Tao Y, Wei P, Wei Q, Li G. Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog. 2018 Mar;57(3):361–369.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

March 2018

Volume

57

Issue

3

Start / End Page

361 / 369

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins
  • Polymorphism, Single Nucleotide
  • Papillomavirus Infections
  • Oropharyngeal Neoplasms
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Humans