Palma Marzia, Ristori Elisabetta, Ricevuto Enrico, Giannini Giuseppe, Gulino Alberto
Department of Experimental Medicine and Pathology, University La Sapienza, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy.
Crit Rev Oncol Hematol. 2006 Jan;57(1):1-23. doi: 10.1016/j.critrevonc.2005.05.003. Epub 2005 Dec 6.
Approximately 5-10% of breast carcinomas and 10% of ovarian carcinomas are ascribable to a genetic susceptibility. Of these, about 40% are related to genetic mutations in the genes BRCA1 and BRCA2. Despite the increasing demand for genetic testing arising from the patients and their relatives, the genetic testing can be offered yet only to individuals belonging to high-risk families in which the probability that there is a germline mutation in a BRCA gene is high and thus cancer occurrence is likely the expression of a highly penetrant genetic predisposition. In this article, we review how the current knowledge on the biological mechanisms underlying BRCA1 and BRCA2 dysfunction may contribute to the understanding of breast and ovarian cancer predisposition. The most currently employed methods for genetic testing are critically overviewed, together with some indications for the interpretation of the test outcome and the clinical management of mutation carriers.
约5%-10%的乳腺癌和10%的卵巢癌可归因于遗传易感性。其中，约40%与BRCA1和BRCA2基因的基因突变有关。尽管患者及其亲属对基因检测的需求不断增加，但目前基因检测仅提供给属于高危家族的个体，这些家族中BRCA基因发生种系突变的概率较高，因此癌症的发生很可能是高度显性遗传易感性的表现。在本文中，我们综述了目前关于BRCA1和BRCA2功能障碍潜在生物学机制的知识如何有助于理解乳腺癌和卵巢癌的易感性。对目前最常用的基因检测方法进行了批判性综述，并给出了一些解读检测结果和对突变携带者进行临床管理的指征。
