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首页> 外文期刊>Carcinogenesis >The role of TP53 and MDM2 polymorphisms in TP53 mutagenesis and risk of non-melanoma skin cancer.
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The role of TP53 and MDM2 polymorphisms in TP53 mutagenesis and risk of non-melanoma skin cancer.

机译:TP53和MDM2多态性在TP53诱变和非黑素瘤皮肤癌风险中的作用。

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摘要

P53 is a key regulatory molecule in the cellular response to ultraviolet radiation, and TP53 mutation is the most common alteration in non-melanoma skin cancer. The MDM2 oncogene negatively regulates p53 protein levels, and both genes have functional polymorphisms that may modify skin cancer risk. Furthermore, prior research suggests that TP53 mutations preferentially occur on the arginine allele to selectively inactivate the p63 pathway. We tested these hypotheses of susceptibility and preferential mutation in non-melanoma skin cancer. The TP53 Arg72Pro and MDM2 309 polymorphisms were genotyped in a population-based case-control study of non-melanoma skin cancer, and TP53 alteration (mutation and immunohistochemistry staining) was evaluated in case tumors. In 902 cases of basal cell carcinoma (BCC), 676 cases of squamous cell carcinoma (SCC) and 812 controls, no association was found between the TP53 polymorphism and risk of non-melanoma skin cancer [odds ratio (OR)(BCC) 0.98, 95% confidence interval (CI) 0.80-1.20; OR(SCC) 0.93, 95% CI 0.75-1.16]. However, carriers of the MDM2 SNP309 G allele did have an elevated risk of non-melanoma skin cancer (OR(BCC) 1.15, 95% CI 0.93-1.42; OR(SCC) 1.29, 95% CI 1.02-1.63). We observed an association between TP53 alterations in the tumors and constitutive TP53 genotype (P < 0.01), with alterations preferentially occurring on the proline allele. Collectively, these data highlight the significant effects of genotype on gene-specific mutation events in carcinogenesis.
机译:P53是细胞对紫外线辐射反应的关键调节分子,而TP53突变是非黑色素瘤皮肤癌中最常见的改变。 MDM2癌基因负调控p53蛋白水平,并且两个基因均具有功能多态性,可能会改变皮肤癌的风险。此外,先前的研究表明,TP53突变优先发生在精氨酸等位基因上,以选择性地使p63途径失活。我们测试了这些非黑色素瘤皮肤癌易感性和优先突变的假说。在一项基于人群的非黑素瘤皮肤癌病例对照研究中,对TP53 Arg72Pro和MDM2 309基因多态性进行了基因分型,并评估了肿瘤病例中TP53的改变(突变和免疫组织化学染色)。在902例基底细胞癌(BCC),676例鳞状细胞癌(SCC)和812对照中,TP53基因多态性与非黑色素瘤皮肤癌风险之间没有关联[比值比(OR)(BCC)0.98 ,95%置信区间(CI)0.80-1.20; OR(SCC)0.93,95%CI 0.75-1.16]。但是,MDM2 SNP309 G等位基因的携带者确实患有非黑色素瘤皮肤癌的风险升高(OR(BCC)1.15,95%CI 0.93-1.42; OR(SCC)1.29,95%CI 1.02-1.63)。我们观察到肿瘤中的TP53改变与组成型TP53基因型之间存在关联(P <0.01),这种改变优先发生在脯氨酸等位基因上。总体而言,这些数据突出了基因型对癌变过程中基因特异性突变事件的重大影响。

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