Schubert E L, Mefford H C, Dann J L, Argonza R H, Hull J, King M C
Department of Medicine, University of Washington, Seattle 98195, USA.
Genet Test. 1997;1(1):41-6. doi: 10.1089/gte.1997.1.41.
The strongest risk factors currently known for inherited predisposition to breast and ovarian cancer are mutations in BRCA1 and BRCA2. Two mutations in BRCA1 and one mutation in BRCA2 have been identified that are present to a particularly high degree in the Ashkenazi Jewish population due to ancient founder effects. To clarify the role of ancient and novel BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population, families with a strong history of breast and ovarian cancer were examined. Seventeen Ashkenazi Jewish families with four or more breast or ovarian cancers were analyzed for ancient and novel mutations in BRCA1 and BRCA2. Ancient mutations existed in 9 families; 7 had the BRCA1 185 del AG mutation, 1 had BRCA1 5382 ins C, and 1 had BRCA2 6174 del T. A novel mutation, BRCA2 6425 del TT, was discovered in 1 of the remaining 8 families. Seven families with four or more cases of breast and ovarian cancer cannot be accounted for by either the ancient or novel mutations. Therefore, ancient mutations in BRCA1 and BRCA2 are present in approximately half of Ashkenazi Jewish families in this series, suggesting the possibility of novel mutations, either in BRCA1, BRCA2, or in currently unidentified gene(s), responsible for the remainder.
目前已知的遗传性乳腺癌和卵巢癌易感性最强的风险因素是BRCA1和BRCA2基因的突变。已鉴定出BRCA1基因的两种突变和BRCA2基因的一种突变，由于古代奠基者效应，这些突变在阿什肯纳兹犹太人群体中呈现出特别高的比例。为了阐明古代和新型BRCA1和BRCA2突变在阿什肯纳兹犹太人群体中的作用，对有乳腺癌和卵巢癌家族史的家庭进行了研究。对17个有4例或更多乳腺癌或卵巢癌病例的阿什肯纳兹犹太家庭进行了BRCA1和BRCA2基因的古代和新型突变分析。9个家庭存在古代突变；7个家庭有BRCA1基因的185delAG突变，1个家庭有BRCA1基因的5382insC突变，1个家庭有BRCA2基因的6174delT突变。在其余8个家庭中的1个家庭中发现了一种新型突变，即BRCA2基因的6425delTT突变。7个有4例或更多乳腺癌和卵巢癌病例的家庭无法用古代或新型突变来解释。因此，在本系列研究中，约一半的阿什肯纳兹犹太家庭存在BRCA1和BRCA2基因的古代突变，这表明其余病例可能是由BRCA1、BRCA2或目前尚未确定的基因中的新型突变所致。
