Role of a p53 polymorphism in the development of human papillomavirus-associated cancer
Role of a p53 polymorphism in the development of human papillomavirus-associated cancer
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作者：
Storey, A;Thomas, M;Banks, L
来源于肿瘤相关的人乳头瘤病毒（hpv）的E6癌蛋白结合并诱导细胞肿瘤抑制蛋白p53的降解。一种常见的多态性发生在p53氨基酸序列中，导致在72位存在脯氨酸或精氨酸，这种多态性对p53对eg介导的降解的易感性的影响已经被研究，发现精氨酸形式的p53明显比脯氨酸形式的p53更容易受到影响。此外，对hpv相关肿瘤患者的等位基因分析显示，与正常人群相比，纯合子精氨酸-72 p53的比例明显过高，这表明精氨酸-72纯合子个体比杂合子个体更容易发生hpv相关肿瘤。因此，精氨酸编码等位基因代表了hpv相关癌症发展的重要危险因素。
The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results In the presence of either a proline or an arginine at position 72, The effect of this polymorphism on the susceptibility of p53 to EG-mediated degradation has been Investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.