Osorio A, Barroso A, Martínez B, Cebrián A, San Román J M, Lobo F, Robledo M, Benítez J
Department of Genetics, Fundación Jiménez Díaz, Madrid, Spain.
Br J Cancer. 2000 Apr;82(7):1266-70. doi: 10.1054/bjoc.1999.1089.
It is estimated that about 5-10% of breast cancer cases may be due to inherited predisposition. Until now, two main susceptibility genes have been identified: BRCA1 and BRCA2. The first linkage and mutational studies suggested that mutations in these two genes would account for the majority of high-risk breast cancer families, but recent studies show how the proportion of families due to BRCA1 or BRCA2 mutations strongly depends on the population and the types of family analyzed. It is now clear that, in the context of families with a modest cancer profile, which are the most commonly found in the clinical practice, the percentage of mutations found is much lower than that suggested by the first studies. In the present study, we analyze a group of 32 Spanish families, which contained at least three cases of female breast cancer (at least one of them diagnosed before the age of 50 years), for the presence of mutations in the BRCA genes. The total proportion of mutations was low (25%), although the percentage of mutations in the BRCA1 and BRCA2 genes was higher, considering the breast and ovarian cancer families and the male breast cancer families respectively. Our results are in agreement with the idea that a great proportion of moderate-risk cancer families could be due to low penetrance susceptibility genes distinct from BRCA1 or BRCA2.
据估计，约5%-10%的乳腺癌病例可能归因于遗传易感性。到目前为止，已确定了两个主要的易感基因：BRCA1和BRCA2。最初的连锁和突变研究表明，这两个基因的突变将占大多数高危乳腺癌家族的病因，但最近的研究表明，由BRCA1或BRCA2突变导致的家族比例在很大程度上取决于所分析的人群和家族类型。现在很清楚，在临床实践中最常见的癌症情况较为温和的家族中，发现的突变百分比远低于最初研究所表明的比例。在本研究中，我们分析了一组32个西班牙家族，这些家族中至少有三例女性乳腺癌（其中至少有一例在50岁之前被诊断出），以检测BRCA基因中是否存在突变。尽管分别考虑乳腺癌和卵巢癌家族以及男性乳腺癌家族时，BRCA1和BRCA2基因的突变百分比更高，但总的突变比例较低（25%）。我们的结果与以下观点一致，即很大一部分中度风险的癌症家族可能归因于不同于BRCA1或BRCA2的低外显率易感基因。
