Association of p73 G4C14-to-A4T14 Polymorphism With Human Papillomavirus Type 16 Status in Squamous Cell Carcinoma of the Head and Neck in Non-Hispanic Whites
Association of p73 G4C14-to-A4T14 Polymorphism With Human Papillomavirus Type 16 Status in Squamous Cell Carcinoma of the Head and Neck in Non-Hispanic Whites
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DOI：
10.1002/cncr.24184
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发表时间：
2009-04-15
期刊：
影响因子：
6.2
通讯作者：
Li, Guojun
中科院分区：
文献类型：
--
作者：
Ji, Xuemei;Sturgis, Erich M.;Li, Guojun
背景技术背景：肿瘤蛋白p73与人乳头瘤病毒16型（HPV-16）癌蛋白E6和E7相互作用，并且p73变异可改变p73蛋白与HPV-16致癌蛋白之间的相互作用，并促进细胞恶性转化。方法：采用正交试验设计在这项病例-病例比较研究中，作者分析了肿瘤标本中的HPV-16状态，并使用202例非西班牙裔白色头颈部鳞状细胞癌（SCCHN）患者血液中的基因组DNA对p73 G4 C14-to-A4 T14多态性进行基因分型。在单变量和多变量logistic回归模型中计算比值比（OR）和95%置信区间（95%CI），以检查SCCHN中p73多态性与HPV-16状态之间的关联。研究结果：与p73 GC/GC基因型相比，AT/AT和GC/AT + AT/AT组合变异基因型与SCCHN患者中HPV-16阳性肿瘤状态显著相关（校正OR，5.32; 95%CI，1.32-21.4;校正OR，1.91; 95%CI，1.03-3.53）。在SCCHN患者中，AT等位基因与HPV-16阳性肿瘤状态之间存在显著的剂量效应关系（趋势检验：P = 0.014）。此外，分层分析表明，HPV-16阳性肿瘤状态与p73 GC/AT + AT/AT基因型组合之间的关联在老年、男性、饮酒者和口咽癌患者的几个亚组中更为明显。结论：p73多态性与SCCHN中的HPV-16状态相关，并且可以作为SCCHN患者，特别是口咽癌患者中HPV-16阳性肿瘤状态的标志物。Cancer 2009;115：1660-8. (C)2009年美国癌症协会。
BACKGROUND: The tumor protein p73 interacts with the human papillomavirus type 16 (HPV-16) oncoproteins E6 and E7, and p73 variation may modify the interaction between p73 protein and HPV-16 oncogenic proteins and contribute to cellular malignant transformation. METHODS: In this case-case comparison study, the authors analyzed HPV-16 status in tumor specimens and genotyped the p73 G4C14-to-A4T14 polymorphism using genomic DNA from blood of 202 non-Hispanic white patients with squamous cell carcinoma of the head and neck (SCCHN). Odds ratio (OR) and 95% confidence intervals (95% Cls) were calculated in univariate and multivariable logistic regression models to examine the association between the p73 polymorphism and HPV-16 status in SCCHN. RESULTS: Compared with the p73 GC/GC genotype, the AT/AT and combined GC/AT + AT/AT variant genotypes were associated significantly with HPV-16-positive tumor status among patients with SCCHN (adjusted OR, 5.32; 95% Cl, 1.32-21.4; adjusted OR, 1.91; 95% Cl, 1.03-3.53, respectively). There was a significant dose-effect relation between the AT allele and HPV-16-positive tumor status in patients with SCCHN (trend test: P = .014). Moreover, the stratified analyses indicated that the association between HPV-16-positive tumor status and the combined p73 GC/AT + AT/AT genotypes was more pronounced among several subgroups of patients who were older, men, ever drinkers, and those with oropharyngeal cancer. CONCLUSIONS: The p73 polymorphism was associated with HPV-16 status in SCCHN and may serve as a marker of positive HPV-16 tumor status in patients with SCCHN, particularly those with oropharyngeal cancer. Cancer 2009;115:1660-8. (C) 2009 American Cancer Society.