p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers
| Autor: | Xuemei Ji, Kristina R. Dahlstrom, Ana C Candia Solari Neumann, Guojun Li, Qingyi Wei, Erich M. Sturgis, Karen Adler-Storthz, John T. Schiller |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Alcohol Drinking Genotype Biology Polymerase Chain Reaction Reference Values Internal medicine Epidemiology medicine Genetic predisposition Humans Genetic variability Codon Aged Human papillomavirus 16 Polymorphism Genetic Patient Selection Papillomavirus Infections Cancer Pharyngeal Neoplasms General Medicine Odds ratio Middle Aged medicine.disease Confidence interval Head and Neck Neoplasms Immunology Carcinoma Squamous Cell Female Mouth Neoplasms Smoking Cessation Viral disease Tumor Suppressor Protein p53 |
| Zdroj: | Carcinogenesis. 29:875-879 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgn039 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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