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P53基因第72位密码子多态性与头颈部鳞状细胞癌风险:一项病例对照研究。

P53 codon 72 polymorphism and risk of squamous cell carcinoma of the head and neck: a case-control study.

作者信息

Shen Hongbing, Zheng Yuxin, Sturgis Erich M, Spitz Margaret R, Wei Qingyi

机构信息

Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Cancer Lett. 2002 Sep 26;183(2):123-30. doi: 10.1016/s0304-3835(02)00117-9.

Abstract

p53 plays an important role in cell-cycle control, as it facilitates DNA repair activities in response to DNA damage. An aberrant cell cycle impairs DNA repair and increases the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg/Pro polymorphism has been suggested to be associated with susceptibility to tobacco-related cancers, but this association remains controversial. In this hospital-based case-control study of 304 patients newly diagnosed with squamous cell carcinoma of the head and neck (SCCHN) and 333 cancer-free controls, we evaluated the association between this p53 polymorphism and the risk of SCCHN. All subjects were non-Hispanic whites, and the controls were frequency-matched to the cases by age (+/-5 years), sex and smoking status. Our results suggested that there was no difference in the distributions of p53 codon 72 genotypes between cases and controls (odds ratio (OR)=1.04, 95% confidence interval (CI) 0.75-1.44 for Pro/Pro vs. Arg/Arg and OR=1.01, 95% CI 0.54-1.91 for Arg/Pro vs. Arg/Arg). However, there was evidence that the Pro allele was associated with an early age of onset of SCCHN. The median ages of onset of SCCHN were 59, 56 and 53 years for Arg/Arg, Arg/Pro and Pro/Pro cases, respectively (P=0.151 among three genotypes; P=0.057 for Pro/Pro and Arg/Pro combined vs. Arg/Arg). The median ages at onset of oral cancers were 62, 57 and 51 years for Arg/Arg, Arg/Pro and Pro/Pro, respectively (P=0.091 among three genotypes; P=0.046 for Pro/Pro vs. Arg/Arg; P=0.066 for Pro/Pro and Arg/Pro combined vs. Arg/Arg). While the results suggest that the P53 codon 72 polymorphism may contribute to oral cancer susceptibility, larger studies are needed to confirm these findings.

摘要

p53在细胞周期调控中发挥重要作用,因为它能促进DNA损伤后的修复活动。异常的细胞周期会损害DNA修复,并增加导致癌变的突变概率。p53密码子72的精氨酸/脯氨酸多态性被认为与烟草相关癌症的易感性有关,但这种关联仍存在争议。在这项基于医院的病例对照研究中,我们纳入了304例新诊断的头颈部鳞状细胞癌(SCCHN)患者和333例无癌对照,评估了这种p53多态性与SCCHN风险之间的关联。所有受试者均为非西班牙裔白人,对照组在年龄(±5岁)、性别和吸烟状况方面与病例进行了频率匹配。我们的结果表明,病例组和对照组之间p53密码子72基因型的分布没有差异(脯氨酸/脯氨酸与精氨酸/精氨酸相比,优势比(OR)=1.04,95%置信区间(CI)为0.75 - 1.44;精氨酸/脯氨酸与精氨酸/精氨酸相比,OR = 1.01,95% CI为0.54 - 1.91)。然而,有证据表明脯氨酸等位基因与SCCHN的发病年龄较早有关。精氨酸/精氨酸、精氨酸/脯氨酸和脯氨酸/脯氨酸病例组的SCCHN发病年龄中位数分别为59岁、56岁和53岁(三种基因型之间P = 0.151;脯氨酸/脯氨酸和精氨酸/脯氨酸合并与精氨酸/精氨酸相比,P = 0.057)。口腔癌的发病年龄中位数在精氨酸/精氨酸、精氨酸/脯氨酸和脯氨酸/脯氨酸组中分别为62岁、57岁和51岁(三种基因型之间P = 0.091;脯氨酸/脯氨酸与精氨酸/精氨酸相比,P = 0.046;脯氨酸/脯氨酸和精氨酸/脯氨酸合并与精氨酸/精氨酸相比,P = 0.066)。虽然结果表明p53密码子72多态性可能与口腔癌易感性有关,但需要更大规模的研究来证实这些发现。

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