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皮肤鳞状细胞癌与p53基因第72位密码子多态性:是否需要进行筛查?

Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?

作者信息

Bastiaens M T, Struyk L, Tjong-A-Hung S P, Gruis N, ter Huurne J, Westendorp R G, Vermeer B J, Bavinck J N, ter Schegget J

机构信息

Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands.

出版信息

Mol Carcinog. 2001 Jan;30(1):56-61. doi: 10.1002/1098-2744(200101)30:1<56::aid-mc1013>3.0.co;2-2.

Abstract

The association between human papillomavirus (HPV)-associated cervical cancer and cutaneous squamous cell carcinoma and codon 72 polymorphism in the p53 gene is not unequivocal. Especially, it is not known whether carriers of the arginine form have an increased risk of cancer that necessitates screening. The alternative is that the polymorphism is a tumor marker instead of a risk factor. We set out a case-control study to determine the risk of squamous cell carcinoma of the skin in individuals with the p53 codon 72 arginine genotype in order to establish the possible need for screening. The distribution of the different p53 codon 72 genotypes was examined in 86 subjects with a history of cutaneous squamous cell carcinoma and in 168 controls. Additionally, 121 subjects who had had histologically proven basal cell carcinoma and 108 subjects who had had non-familial malignant melanoma were tested. p53 polymorphism was evaluated by polymerase chain reaction (PCR) using DNA samples from peripheral blood lymphocytes. In a subgroup of patients with squamous cell carcinoma and controls, the presence of epidermodyplasia verruciformis human papillomavirus (EV-HPV) DNA was determined in plucked eyebrow hair. Differences in the distributions of the genotypes among cases and controls were calculated, and univariate and multivariate analyses were performed to assess the risk to develop cutaneous squamous cell carcinoma in the presence of the p53 codon 72 arginine genotype. Frequency distributions of the three different genotypes (homozygous for the arginine allele, heterozygous for the two alleles, and homozygous for the proline allele) were similar among the squamous cell carcinoma group and the control group: 47.1%, 46.0% and 6.9% versus 47.8%, 45.8% and 6.4%, respectively. Statistical analysis showed no significant differences between these groups. In patients with squamous cell carcinoma and controls who harbored EV-HPV DNA in their plucked eyebrow hair, similar results were obtained. The distributions of the p53 codon 72 genotypes in the basal cell carcinoma and malignant melanoma group were also not significantly different from the control group. p53 codon 72 arginine homozygosity does not appear to represent a significant risk factor for cutaneous squamous cell carcinoma and screening seems not to be indicated. Mol. Carcinog. 30:56-61, 2001.

摘要

人乳头瘤病毒(HPV)相关的宫颈癌与皮肤鳞状细胞癌以及p53基因第72位密码子多态性之间的关联并不明确。尤其是,精氨酸形式的携带者患癌风险是否增加以至于需要进行筛查尚不清楚。另一种情况是,这种多态性是一种肿瘤标志物而非风险因素。我们开展了一项病例对照研究,以确定p53基因第72位密码子为精氨酸基因型的个体患皮肤鳞状细胞癌的风险,从而确定是否可能需要进行筛查。我们检测了86例有皮肤鳞状细胞癌病史的受试者和168例对照者中不同p53基因第72位密码子基因型的分布情况。此外,还检测了121例经组织学证实患有基底细胞癌的受试者以及108例患有非家族性恶性黑色素瘤的受试者。使用外周血淋巴细胞的DNA样本通过聚合酶链反应(PCR)评估p53基因多态性。在鳞状细胞癌患者和对照者的一个亚组中,通过拔除的眉毛毛发检测疣状表皮发育不良人乳头瘤病毒(EV-HPV)DNA的存在情况。计算病例组和对照组中基因型分布的差异,并进行单因素和多因素分析,以评估在存在p53基因第72位密码子精氨酸基因型的情况下发生皮肤鳞状细胞癌的风险。鳞状细胞癌组和对照组中三种不同基因型(精氨酸等位基因纯合子、两个等位基因杂合子和脯氨酸等位基因纯合子)的频率分布相似:分别为47.1%、46.0%和6.9%,以及47.8%、45.8%和6.4%。统计分析表明这些组之间无显著差异。在拔除的眉毛毛发中携带EV-HPV DNA的鳞状细胞癌患者和对照者中,也得到了类似的结果。基底细胞癌组和恶性黑色素瘤组中p53基因第72位密码子基因型的分布与对照组相比也无显著差异。p53基因第72位密码子精氨酸纯合性似乎并非皮肤鳞状细胞癌的显著风险因素,似乎无需进行筛查。《分子致癌学》30:56 - 61,2001年。

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