Molecular analysis of the BRCA1 and BRCA2 genes in 32 breast and/or ovarian cancer Spanish families

It is estimated that about 5-10% of breast cancer cases may be due to inher ited predisposition. Until now, two main susceptibility genes have been ide ntified: BRCA1 and BRCA2. The first linkage and mutational studies suggeste d 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 tha n that suggested by the first studies. In the present study, we analyze a g roup 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 m utations was low (25%), although the percentage of mutations in the BRCA1 a nd BRCA2 genes was higher, considering the breast and ovarian cancer famili es and the male breast cancer families respectively. Our results are in agr eement with the idea that a great proportion of moderate-risk cancer famili es could be due to low penetrance susceptibility genes distinct from BRCA I or BRCA2. (C) 2000 Cancer Research Campaign.