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P53基因第72位密码子多态性、人乳头瘤病毒感染及其与口腔癌易感性的相互作用

P53 codon 72 polymorphism, human papillomavirus infection, and their interaction to oral carcinoma susceptibility.

作者信息

Hou Jun, Gu Ying, Hou Wei, Wu Song, Lou Yin, Yang Wenyu, Zhu Ling, Hu Yukun, Sun Ming, Xue Haowei

机构信息

Department of Stomatology, the First Affiliated Hospital of the Anhui Medical University, Hefei, Anhui, 230032, China.

Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY, 11794, USA.

出版信息

BMC Genet. 2015 Jun 30;16:72. doi: 10.1186/s12863-015-0235-7.

Abstract

BACKGROUND

Tumor suppressor gene p53 plays an important role in the maintenance of the genomic integrity, and mutation in the gene may alter an individual's susceptibility to various carcinomas. P53 Arg72Pro or codon 72 polymorphism has been indicated to increase the risk of developing certain cancers such as bladder cancer and cervical cancer. Human papillomavirus (HPV) infection has been shown as a risk factor for certain cancers such as cervical cancer and oral cancer as well, and the HPV oncoprotein E6 may induce the degradation of p53 function. However, the association between p53 Arg72Pro polymorphism and the risk of oral cancer with HPV infection remains inconclusive. Therefore, this meta-analysis involving 5,614 participants was performed to investigate the relations among the p53 Arg72Pro polymorphism, HPV infection, and the risk of developing oral cancer.

RESULTS

A search of the literature by PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted to identify studies based on the inclusion and exclusion criteria. Odds ratios with 95% confidence intervals were combined using a random-effect model or a fixed-effect model. The current study was conducted with 13 studies consisting of 2,413 cases and 3,201 controls. Neither overall analysis nor stratified analyses detected any obvious evidence of association between p53 Arg72Pro polymorphism and oral cancer susceptibility in all genetic models. However, a significant association between p53 Arg72Pro polymorphism and the risk of oral cancer with HPV infection was detected in the Arg/Arg vs. Arg/Pro + Pro/Pro model.

CONCLUSION

In the current meta-analysis which used the quantitative data synthesis for the first time, our study demonstrated that p53 Arg72Pro polymorphism together with HPV infection might jointly alter an individual's susceptibility to the risk of oral cancer. Our results suggested that p53 Arg72Pro polymorphism may partly contribute to the pathogenesis of oral cancer development.

摘要

背景

肿瘤抑制基因p53在维持基因组完整性方面发挥着重要作用,该基因的突变可能会改变个体对各种癌症的易感性。已表明p53 Arg72Pro或密码子72多态性会增加患某些癌症的风险,如膀胱癌和宫颈癌。人乳头瘤病毒(HPV)感染也已被证明是某些癌症的危险因素,如宫颈癌和口腔癌,并且HPV癌蛋白E6可能会诱导p53功能的降解。然而,p53 Arg72Pro多态性与HPV感染导致口腔癌风险之间的关联仍无定论。因此,本荟萃分析纳入了5614名参与者,以研究p53 Arg72Pro多态性、HPV感染与患口腔癌风险之间的关系。

结果

通过PubMed、Embase、Web of Science和中国国家知识基础设施数据库检索文献,以确定符合纳入和排除标准的研究。使用随机效应模型或固定效应模型合并95%置信区间的比值比。本研究纳入了13项研究,共2413例病例和3201例对照。在所有遗传模型中,总体分析和分层分析均未发现p53 Arg72Pro多态性与口腔癌易感性之间存在明显关联的证据。然而,在Arg/Arg与Arg/Pro + Pro/Pro模型中,检测到p53 Arg72Pro多态性与HPV感染导致口腔癌的风险之间存在显著关联。

结论

在本次首次使用定量数据合成的荟萃分析中,我们的研究表明p53 Arg72Pro多态性与HPV感染可能共同改变个体患口腔癌的易感性。我们的结果表明,p53 Arg72Pro多态性可能在一定程度上促成了口腔癌发生的病理过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56b/4484699/049769aca097/12863_2015_235_Fig1_HTML.jpg

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