Cornelis R S, Vasen H F, Meijers-Heijboer H, Ford D, van Vliet M, van Tilborg A A, Cleton F J, Klijn J G, Menko F H, Meera Khan P
Department of Human Genetics, University of Leiden, The Netherlands.
Hum Genet. 1995 May;95(5):539-44. doi: 10.1007/BF00223866.
We searched for criteria that could indicate breast cancer families with a high prior probability of being caused by the breast/ovarian cancer susceptibility locus BRCA1 on chromosome 17. To this end, we performed a linkage study with 59 consecutively collected Dutch breast cancer families, including 16 with at least one case of ovarian cancer. We used an intake cut-off of at least three first-degree relatives with breast and/or ovarian cancer at any age. Significant evidence for linkage was found only among the 13 breast cancer families with a mean age at diagnosis of less than 45 years. An unexpectedly low proportion of the breast-ovarian cancer families were estimated to be linked to BRCA1, which could be due to a founder effect in the Dutch population. Given the expected logistical problems in clinical management now that BRCA1 has been identified, we propose an interim period in which only families with a strong positive family history for early onset breast and/or ovarian cancer will be offered BRCA1 mutation testing.
我们寻找了一些标准，这些标准可用于指示那些极有可能由位于17号染色体上的乳腺癌/卵巢癌易感基因座BRCA1所引发的乳腺癌家族。为此，我们对连续收集的59个荷兰乳腺癌家族进行了连锁研究，其中包括16个至少有1例卵巢癌病例的家族。我们采用的纳入标准是，任何年龄段至少有三名患乳腺癌和/或卵巢癌的一级亲属。仅在诊断时平均年龄小于45岁的13个乳腺癌家族中发现了显著的连锁证据。据估计，乳腺癌-卵巢癌家族中与BRCA1连锁的比例出乎意料地低，这可能是由于荷兰人群中的奠基者效应。鉴于BRCA1已被确定，目前临床管理中预计会出现后勤问题，我们提议设立一个过渡阶段，在此期间，仅为那些有早发性乳腺癌和/或卵巢癌强阳性家族史的家族提供BRCA1突变检测。
