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Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck.

Publication ,  Journal Article
Yu, H; Huang, Y-J; Liu, Z; Wang, L-E; Li, G; Sturgis, EM; Johnson, DG; Wei, Q
Published in: Mol Carcinog
September 2011

Both p53 tumor suppressor and murine double minute 2 (MDM2) oncoprotein are crucial in carcinogenesis. We hypothesized that MDM2 promoter single nucleotide polymorphisms (SNPs) SNP309 T > G, A2164G, and p53 codon 72 are associated with risk and age at onset of squamous cell carcinoma of head and neck (SCCHN). We genotyped these SNPs in a study of 1,083 Caucasian SCCHN cases and 1,090 cancer-free controls. Although none of these SNPs individually had a significant effect on risk of SCCHN, nor did their combined putative risk genotypes (i.e., MDM2 SNP309 GT + GG, 2164 AA, and p53 codon 72 CC), we found that individuals with two to three risk genotypes had significantly increased risk of non-oropharyngeal cancer (OR = 1.42; 95% CI = 1.07-1.88). This increased risk was more pronounced among young subjects, men, smokers, and drinkers. In addition, female patients carrying the MDM2 SNP309 GT and GG genotypes showed a 3-yr (56.7 yr) and 9-yr (51.2 yr) earlier age at onset of non-oropharyngeal cancer (P(trend) = 0.007), respectively, compared with those carrying the TT genotype (60.1 yr). The youngest age (42.5 yr) at onset of non-oropharyngeal cancer was observed in female patients with the combined MDM2 SNP309 GG and p53 codon 72 CC genotypes. The findings suggest that MDM2 SNP309, A2164G, and p53 codon 72 SNPs may collectively contribute to non-oropharyngeal cancer risk and that MDM2 SNP309 individually or in combination with p53 codon 72 may accelerate the development of non-oropharyngeal cancer in women. Further studies with large sample sizes are warranted to validate these results.

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

September 2011

Volume

50

Issue

9

Start / End Page

697 / 706

Location

United States

Related Subject Headings

  • Young Adult
  • Proto-Oncogene Proteins c-mdm2
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Polymorphism, Restriction Fragment Length
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
 

Citation

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Yu, H., Huang, Y.-J., Liu, Z., Wang, L.-E., Li, G., Sturgis, E. M., … Wei, Q. (2011). Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog, 50(9), 697–706. https://doi.org/10.1002/mc.20806
Yu, Hongping, Yu-jing Huang, Zhensheng Liu, Li-E Wang, Guojun Li, Erich M. Sturgis, David G. Johnson, and Qingyi Wei. “Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck.Mol Carcinog 50, no. 9 (September 2011): 697–706. https://doi.org/10.1002/mc.20806.
Yu H, Huang Y-J, Liu Z, Wang L-E, Li G, Sturgis EM, et al. Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog. 2011 Sep;50(9):697–706.
Yu, Hongping, et al. “Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck.Mol Carcinog, vol. 50, no. 9, Sept. 2011, pp. 697–706. Pubmed, doi:10.1002/mc.20806.
Yu H, Huang Y-J, Liu Z, Wang L-E, Li G, Sturgis EM, Johnson DG, Wei Q. Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog. 2011 Sep;50(9):697–706.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

September 2011

Volume

50

Issue

9

Start / End Page

697 / 706

Location

United States

Related Subject Headings

  • Young Adult
  • Proto-Oncogene Proteins c-mdm2
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Polymorphism, Restriction Fragment Length
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans