Neuhausen S L, Ostrander E A
Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City 84108, USA.
Genet Test. 1997;1(2):75-83. doi: 10.1089/gte.1997.1.75.
BRCA1 and BRCA2, genes predisposing to early-onset breast cancer, have been isolated and are characterized for mutation spectrum, risks of cancer, and function. The different methodologies to screen for mutations in BRCA1 and BRCA2 are briefly discussed including DNA-based methodologies and potential new assays. The numbers and types of mutations identified to date are described, including the problems of ascribing risk to missense mutations. Recurring, possibly founding mutations have been identified in several populations including Ashkenazi Jews, Icelanders, Swedes, and African Americans. From population-based studies, estimates are that 6%-10% of breast cancers are due to mutations in BRCA1 and BRCA2. Knowledge of mutation status raises additional questions including the interpretation of negative tests and the risks of breast and other cancers associated with positive test results.
乳腺癌易感基因BRCA1和BRCA2已被分离出来，并对其突变谱、癌症风险及功能进行了表征。简要讨论了筛查BRCA1和BRCA2突变的不同方法，包括基于DNA的方法和潜在的新检测方法。描述了迄今为止鉴定出的突变数量和类型，包括将风险归因于错义突变的问题。在包括德系犹太人、冰岛人、瑞典人和非裔美国人在内的几个群体中发现了反复出现的、可能是奠基性的突变。基于人群的研究估计，6%-10%的乳腺癌是由BRCA1和BRCA2突变引起的。突变状态的知识引发了更多问题，包括阴性检测结果的解读以及阳性检测结果与乳腺癌和其他癌症的风险。
