p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers
p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers
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DOI：
10.1093/carcin/bgn039
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发表时间：
2008-04-01
期刊：
影响因子：
4.7
通讯作者：
Li, Guojun
中科院分区：
文献类型：
--
作者：
Ji, Xuemei;Neumann, Ana S.;Li, Guojun
抑癌基因p53蛋白可被人乳头瘤病毒（HPV）E6癌蛋白结合、降解和失活。p53蛋白对这种癌蛋白的易感性可能受到p53密码子72多态性的影响，但这种多态性在HPV 16相关的口咽鳞状细胞癌（SCCOP）的发展中的作用尚未确定。为了研究p53密码子72多态性在HPV 16相关SCCOP风险中的作用，我们对188例新诊断SCCOP的非西班牙裔白色患者和342例无癌症对照受试者进行了一项基于医院的病例对照研究，这些受试者的年龄（+/- 5岁）、性别、吸烟状况和饮酒状况频率匹配。我们发现HPV 16血清阳性与SCCOP风险增加相关[校正比值比（OR），5.7; 95%置信区间（CI），3.7-8.7]，尤其是在从不吸烟者中（校正OR，14.1; 95% CI，6.0-32.9）和p53密码子72变异基因型[精氨酸（Arg）/脯氨酸（Pro）和Pro/Pro]受试者中（校正OR，9.2; 95% CI，4.7-17.7）。p53密码子72多态性与HPV 16血清学阳性之间也存在显著的乘性交互作用（P = 0.05）。在从不吸烟的人群中，HPV 16血清阳性和p53密码子72变异基因型（Arg/Pro + Pro/Pro）的SCCOP风险特别高（校正OR，22.5; 95%CI，4.8-106.2）。这些发现表明，p53密码子72变异基因型改变了HPV 16相关SCCOP的风险，并可能是HPV 16相关SCCOP遗传易感性的标志物，特别是在从不吸烟者中。
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.