Carcinogenesis Advance Access originally published online on August 13, 2008
Carcinogenesis 2008 29(11):2120-2125; doi:10.1093/carcin/bgn191
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Combined effects of the p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer in never-smokers
1 Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
2 Department of Otolaryngology, Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
3 Department of Epidemiology
4 Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
* To whom correspondence should be addressed. Department of Head and Neck Surgery, Unit 441, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel: +1 713 792 0227; Fax: +1 713 794 4662; Email: gli{at}mdanderson.org
Because p53 and p73 are associated with critical cellular processes and can be inactivated or degraded by the human papillomavirus (HPV) E6 oncoprotein, we investigated the combined effects of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer. We analyzed genotype data from 326 patients with squamous cell carcinoma of the oral cavity or oropharynx and 349 cancer-free controls. We found that HPV16 seropositivity was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.42; 95% confidence interval (CI), 2.28–5.13], especially among never-smokers (adjusted OR, 8.20; 95% CI, 3.66–18.4) and subjects with variant genotypes [adjusted OR for p53 Arg/Pro + Pro/Pro (Pro carriers), 5.00; 95% CI, 2.72–9.21; adjusted OR for p73 GC/AT + AT/AT (AT carriers), 3.83; 95% CI, 1.98–7.41]. HPV16 seropositivity was also associated with an significantly increased risk of oral cancer in all three risk groups with combined genotypes [adjusted ORs (95% CIs) were 2.28 (1.15–4.54) for p53 Arg/Arg and p73 GC/GC, the low-risk group; 3.97 (2.14–7.36) for p53 Arg/Arg and p73 AT carriers or p53 Pro carriers and p73 GC/GC, the medium-risk group and 5.11 (2.00–13.0) for p53 Pro carriers and p73 AT carriers, the high-risk group]. Moreover, HPV16-seropositive never-smokers in the high-risk group exhibited an 
11-fold greater risk of oral cancer (adjusted OR, 11.3; 95% CI, 1.22–106.0) than did HPV16-seronegative never-smokers in the low-risk group. These findings suggest that the combined variants of p53 and p73 significantly increase the risk of HPV16-associated oral cancer, especially among never-smokers.
Abbreviations: CI, confidence interval; HPV, human papillomavirus; OR, odds ratio; PCR, polymerase chain reaction
Received June 17, 2008; revised July 22, 2008; accepted August 7, 2008.