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[乳腺癌遗传学。BRCA1和BRCA2:疾病易感性的主要基因]

[Breast cancer genetics. BRCA1 and BRCA2: the main genes for disease predisposition].

作者信息

Ruiz-Flores P, Calderón-Garcidueñas A L, Barrera-Saldaña H A

机构信息

Laboratorio de Genética Molecular de la ULIEG, México.

出版信息

Rev Invest Clin. 2001 Jan-Feb;53(1):46-64.

Abstract

Breast cancer is among the most common world cancers. In Mexico this neoplasm has been progressively increasing since 1990 and is expected to continue. The risk factors for this disease are age, some reproductive factors, ionizing radiation, contraceptives, obesity and high fat diets, among other factors. The main risk factor for BC is a positive family history. Several families, in which clustering but no mendelian inheritance exists, the BC is due probably to mutations in low penetrance genes and/or environmental factors. In families with autosomal dominant trait, the BRCA1 and BRCA2 genes are frequently mutated. These genes are the two main BC susceptibility genes. BRCA1 predispose to BC and ovarian cancer, while BRCA2 mutations predispose to BC in men and women. Both are long genes, tumor suppressors, functioning in a cell cycle dependent manner, and it is believed that both switch on the transcription of several genes, and participate in DNA repair. The mutations profile of these genes is known in developed countries, while in Latin America their search has just began. A multidisciplinary group most be responsible of the clinical management of patients with mutations in BRCA1 and BRCA2, and the risk assignment and Genetic counseling most be done carefully.

摘要

乳腺癌是世界上最常见的癌症之一。在墨西哥,自1990年以来这种肿瘤一直在逐渐增加,并且预计还会继续增加。该疾病的风险因素包括年龄、一些生殖因素、电离辐射、避孕药、肥胖和高脂肪饮食等。乳腺癌的主要风险因素是家族史阳性。在一些家族中,存在聚集现象但不存在孟德尔遗传,乳腺癌可能是由于低外显率基因的突变和/或环境因素导致的。在具有常染色体显性特征的家族中,BRCA1和BRCA2基因经常发生突变。这些基因是两个主要的乳腺癌易感基因。BRCA1易患乳腺癌和卵巢癌,而BRCA2突变易使男性和女性患乳腺癌。两者都是长基因,属于肿瘤抑制基因,以细胞周期依赖的方式发挥作用,并且人们认为它们都会开启几个基因的转录,并参与DNA修复。在发达国家,这些基因的突变情况是已知的,而在拉丁美洲,对它们的研究才刚刚开始。一个多学科小组必须负责对BRCA1和BRCA2基因发生突变的患者进行临床管理,并且必须谨慎地进行风险评估和遗传咨询。

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