Carcinogenesis Advance Access originally published online on February 6, 2008
Carcinogenesis 2008 29(4):875-879; doi:10.1093/carcin/bgn039
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p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers
1 Department of Head and Neck Surgery
2 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
3 Dental Division of the Royal Children's Hospital, Melbourne 3052, Australia
4 Department of Diagnostic Sciences, The University of Texas Health Science Center-Dental Branch, Houston, TX 77030, USA
5 Department of Genetics and Developmental Medicine, University of Washington, Seattle, WA 98195, USA
6 Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
* To whom correspondence should be addressed. Tel: +1 713 792 0227; Fax: +1 713 794 4662; Email: gli{at}mdanderson.org
The tumor suppressor p53 protein can be bound, degraded and inactivated by the human papillomavirus (HPV) E6 oncoprotein. The p53 protein's susceptibility to this oncoprotein may be influenced by the p53 codon 72 polymorphism, but the role of such a polymorphism in the development of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP) has not been established. To investigate the role of the p53 codon 72 polymorphism in the risk of HPV16-associated SCCOP, we conducted a hospital-based case–control study of 188 non-Hispanic white patients with newly diagnosed SCCOP and 342 cancer-free control subjects frequency matched by age (±5 years), sex, tobacco smoking status and alcohol drinking status. We found that HPV16 seropositivity was associated with an increased risk of SCCOP [adjusted odds ratio (OR), 5.7; 95% confidence interval (CI), 3.7–8.7], especially among never-smokers (adjusted OR, 14.1; 95% CI, 6.0–32.9) and among subjects with the p53 codon 72 variant genotypes [Arginine (Arg)/Proline (Pro) and Pro/Pro] (adjusted OR, 9.2; 95% CI, 4.7–17.7). A significant multiplicative interaction on the risk of SCCOP was also found between the p53 codon 72 polymorphism and HPV16 seropositivity (P = 0.05). Among never-smokers, the risk of SCCOP for those who had both HPV16 seropositivity and p53 codon 72 variant genotypes (Arg/Pro + Pro/Pro) was particularly high (adjusted OR, 22.5; 95% CI, 4.8–106.2). These findings suggest that p53 codon 72 variant genotypes modify the risk of HPV16-associated SCCOP and may be markers of genetic susceptibility to HPV16-associated SCCOP, especially among never-smokers.
Abbreviations: Arg, Arginine; CI, confidence interval; HPV, human papillomavirus; MDACC, M. D. Anderson Cancer Center; OR, odds ratio; PCR, polymerase chain reaction; Pro, Proline; SCCOP, squamous cell carcinoma of the oropharynx
Received October 22, 2007; revised January 10, 2008; accepted January 29, 2008.
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  X. Chen, E. M. Sturgis, A. K. El-Naggar, Q. Wei, and G. Li Combined effects of the p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer in never-smokers Carcinogenesis, November 1, 2008; 29(11): 2120 - 2125. [Abstract] [Full Text] [PDF]
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