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TP53突变作为拉丁美洲癌症流行病学的生物标志物:当前的认识与展望

TP53 mutations as biomarkers for cancer epidemiology in Latin America: current knowledge and perspectives.

作者信息

de Moura Gallo Claudia Vitória, Azevedo E Silva Mendonça Gulnar, de Moraes Emanuela, Olivier Magali, Hainaut Pierre

机构信息

Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Mutat Res. 2005 May;589(3):192-207. doi: 10.1016/j.mrrev.2005.01.002. Epub 2005 Mar 31.

Abstract

Due to particular social and economical development, and to the impact of globalization of lifestyles, Latin America shows a superposition of cancers that are frequent in low resource countries (gastric, oesophageal squamous cell and cervical cancers) and high resource countries (cancers of breast, colon and rectum, lung and prostate). Latin America thus offers opportunities for investigating the impact on changing lifestyle patterns on the occurrence of cancer. At the molecular level, mutations in the tumor suppressor gene TP53 are common in many cancers and their distribution can be informative of the nature of the mutagenic mechanisms, thus giving clues to cancer etiology and molecular pathogenesis. However most of the data available are derived from studies in industrialized countries. In this review, we discuss current trends on cancer occurrence in Latin American countries, and we review the literature available on TP53 mutations and polymorphisms in patients from Latin America. Overall, a total of 285 mutations have been described in 1213 patients in 20 publications, representing 1.5% of the total number of mutations reported world-wide. Except for hematological cancers, TP53 mutation frequencies are similar to those reported in other regions of the world. The only tumor site presenting significant differences in mutation pattern as compared to other parts of the world is colon and rectum. However, this difference is based on a single study with 35 patients. Recently, a characteristic TP53 mutation at codon 337 (R337H) has been identified in the germline of children with adrenocortical carcinoma in Southern Brazil. Further and better focused analyses of TP53 mutation patterns in the context of epidemiological studies, should help to improve our understanding of cancer etiology in order to develop appropriate health policies and public health programs in Latin America.

摘要

由于特定的社会经济发展以及生活方式全球化的影响,拉丁美洲呈现出低资源国家常见癌症(胃癌、食管鳞状细胞癌和宫颈癌)与高资源国家常见癌症(乳腺癌、结肠直肠癌、肺癌和前列腺癌)叠加的情况。因此,拉丁美洲为研究生活方式模式变化对癌症发生的影响提供了机会。在分子水平上,肿瘤抑制基因TP53的突变在许多癌症中很常见,其分布可以反映诱变机制的性质,从而为癌症病因和分子发病机制提供线索。然而,现有的大多数数据来自工业化国家的研究。在本综述中,我们讨论了拉丁美洲国家癌症发生的当前趋势,并回顾了拉丁美洲患者中TP53突变和多态性的现有文献。总体而言,20篇出版物中1213名患者共描述了285个突变,占全球报告突变总数的1.5%。除血液系统癌症外,TP53突变频率与世界其他地区报告的频率相似。与世界其他地区相比,唯一在突变模式上存在显著差异的肿瘤部位是结肠和直肠。然而,这种差异仅基于一项对35名患者的研究。最近,在巴西南部肾上腺皮质癌儿童的种系中发现了密码子337(R337H)处的一种特征性TP53突变。在流行病学研究的背景下,对TP53突变模式进行更深入、更有针对性的分析,应有助于提高我们对癌症病因的理解,以便在拉丁美洲制定适当的卫生政策和公共卫生计划。

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