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
Article first published online: 7 JUN 2011
Copyright © 2011 Wiley-Liss, Inc.
Volume 50, Issue 9, pages 697–706, September 2011
How to Cite
Yu, H., Huang, Y.-j., Liu, Z., Wang, L.-E., Li, G., Sturgis, E. M., Johnson, D. G. and 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: 697–706. doi: 10.1002/mc.20806
- Issue published online: 21 JUL 2011
- Article first published online: 7 JUN 2011
- Manuscript Accepted: 3 MAY 2011
- Manuscript Revised: 19 APR 2011
- Manuscript Received: 25 JAN 2011
- squamous cell carcinoma of the head and neck;
- age at onset
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 (Ptrend = 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. © 2011 Wiley-Liss, Inc.