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p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx
Article first published online: 9 MAY 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 12, pages 2461–2465, 15 June 2007
How to Cite
Perrone, F., Mariani, L., Pastore, E., Orsenigo, M., Suardi, S., Marcomini, B., DaRiva, L., Licitra, L., Carbone, A., Pierotti, M. A. and Pilotti, S. (2007), p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx. Cancer, 109: 2461–2465. doi: 10.1002/cncr.22702
- Issue published online: 4 JUN 2007
- Article first published online: 9 MAY 2007
- Manuscript Accepted: 20 FEB 2007
- Manuscript Revised: 2 FEB 2007
- Manuscript Received: 26 SEP 2006
- Italian Association for Cancer Research and Ministero della Salute Ricerca Finalizzata 2004
- p53 polymorphism;
- cancer risk;
- high-risk human papillomavirus (HR-HPV)-positive;
- oropharyngeal squamous cell carcinoma
Tobacco smoking, alcohol abuse, and high-risk human papillomavirus (HPV) are risk factors in the etiology of oropharyngeal squamous cell carcinomas (SCCs). The TP53 polymorphism, in which an arginine (R) is changed to proline (P) at codon 72, is functionally significant and could therefore be a predisposing genetic defect.
The aim of the study was to investigate the role of codon 72 polymorphism by means of double gradient-denaturing gel electrophoresis in 77 oropharyngeal SCC patients including 33 TP53 mutated and 16 HPV-16-positive cases. The controls consisted of 141 consecutive healthy blood donors.
The cases and controls showed significantly different genotype distribution (P = .0005): the frequencies of the RR, RP, and PP genotypes among the cases were, respectively, 81.8%, 10.4%, and 7.8%, as opposed to 59.6%, 33.3%, and 7.1% among the controls, in agreement with the Hardy-Weinberg equilibrium (P = .35). The PP genotype was significantly overrepresented among females (22.2% vs 3.4%; P = .0243) and in HPV-16-positive cases (25.0% vs 3.3%; P = .0152). No segregation was found between either of the codon 72 genotypes and age or TP53 mutations.
The significantly lower frequency of the RP genotype in the patients as a whole suggests that it has a protective effect on oropharyngeal SCCs. Moreover, the PP genotype may be a risk factor for the development of oropharyngeal SCC by females and the development of HPV-16-related SCC, although the findings need to be validated in a larger number of tumors. Cancer 2007. © 2007 American Cancer Society.