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第72位密码子处的p53基因多态性——它会增加中欧人群患宫颈鳞状上皮内病变和浸润性宫颈癌的风险吗?

p53 polymorphism at codon 72--does it constitute a risk for squamous intraepithelial lesions and invasive cancer of the cervix in Central Europeans?

作者信息

Kucera E, Tong D, Reinthaller A, Leodolter S, Zeillinger R, Sliutz G

机构信息

Department of Obstetrics and Gynecology, University of Vienna, Medical School, General Hospital, Austria.

出版信息

Wien Klin Wochenschr. 2000 Sep 29;112(18):817-20.

Abstract

BACKGROUND

Polymorphisms of the tumour suppresser gene p53 especially at codon 72 are suspected to be associated with an increased risk for malignant transformation. In invasive cervical cancer, the arginine form of the p53 gene is estimated to be more susceptible to degradation mediated by tumour-associated human papilloma viruses (HPV) than the proline form.

METHODS

To test the prevalence of p53 polymorphism at codon 72 in 133 healthy women, 50 patients suffering from squamous intraepithelial lesions of the cervix (SIL), and 105 patients with invasive cervical cancer, we developed a polymerase chain reaction (PCR) and microtiter plate-based hybridisation assay. Furthermore, we tested whether the two p53 isoforms increased the risk of developing cervical cancer.

RESULTS

The proportions of individual homozygous for arginine, homozygous for proline and heterozygous for arginine and proline in the investigated patient groups did not significantly deviate from the Hardy-Weinberg equilibrium. We found no increased risk of developing cervical cancer in respect to p53 polymorphism, independent of histological diagnosis.

DISCUSSION

In conformity with other study groups, our findings do not support the hypothesis that the p53 polymorphism at codon 72 is important in determining an increased risk of developing HPV-associated SIL or invasive cervical cancer in Central Europeans.

摘要

背景

肿瘤抑制基因p53的多态性,尤其是第72密码子处的多态性,被怀疑与恶性转化风险增加有关。在浸润性宫颈癌中,p53基因的精氨酸形式比脯氨酸形式更容易受到肿瘤相关人乳头瘤病毒(HPV)介导的降解作用。

方法

为了检测133名健康女性、50名患有宫颈鳞状上皮内病变(SIL)的患者以及105名浸润性宫颈癌患者中第72密码子处p53多态性的发生率,我们开发了一种基于聚合酶链反应(PCR)和微量滴定板的杂交检测方法。此外,我们还检测了两种p53异构体是否会增加患宫颈癌的风险。

结果

在被调查的患者组中,精氨酸纯合子、脯氨酸纯合子以及精氨酸和脯氨酸杂合子的比例与哈迪-温伯格平衡无显著偏差。我们发现,无论组织学诊断如何,p53多态性与患宫颈癌风险增加无关。

讨论

与其他研究组一致,我们的研究结果不支持以下假设:在中欧人群中,第72密码子处的p53多态性在确定HPV相关的SIL或浸润性宫颈癌风险增加方面具有重要意义。

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