Ji Xuemei, Neumann Ana S, Sturgis Erich M, Adler-Storthz Karen, Dahlstrom Kristina R, Schiller John T, Wei Qingyi, Li Guojun
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Carcinogenesis. 2008 Apr;29(4):875-9. doi: 10.1093/carcin/bgn039. Epub 2008 Feb 6.
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.
肿瘤抑制蛋白p53可被人乳头瘤病毒（HPV）E6癌蛋白结合、降解并失活。p53蛋白对这种癌蛋白的易感性可能受p53密码子72多态性的影响，但这种多态性在人乳头瘤病毒16型（HPV16）相关口咽鳞状细胞癌（SCCOP）发生发展中的作用尚未明确。为了研究p53密码子72多态性在HPV16相关SCCOP风险中的作用，我们开展了一项基于医院的病例对照研究，纳入188例新诊断的非西班牙裔白人SCCOP患者和342例年龄（±5岁）、性别、吸烟状况和饮酒状况频率匹配的无癌对照者。我们发现，HPV16血清学阳性与SCCOP风险增加相关[校正比值比（OR）为5.7；95%置信区间（CI）为3.7 - 8.7]，尤其在从不吸烟者中（校正OR为14.1；95% CI为6.0 - 32.9）以及p53密码子72变异基因型[精氨酸（Arg）/脯氨酸（Pro）和Pro/Pro]的受试者中（校正OR为9.2；95% CI为4.7 - 17.7）。p53密码子72多态性与HPV16血清学阳性之间在SCCOP风险上也存在显著的相乘交互作用（P = 0.05）。在从不吸烟者中，同时具有HPV16血清学阳性和p53密码子72变异基因型（Arg/Pro + Pro/Pro）者的SCCOP风险特别高（校正OR为22.5；95% CI为4.8 - 106.2）。这些发现提示，p53密码子72变异基因型改变了HPV16相关SCCOP的风险，可能是HPV16相关SCCOP遗传易感性的标志物，尤其在从不吸烟者中。
