Genome-wide scanning for linkage in 56 Dutch breast cancer families selected for a minimal probability of being due to BRCA1 or BRCA2

Excerpt

A conventional model of inherited breast cancer susceptibility is that disease risks are affected by mutations in a small number of genes causing a high risk of the disease and by a larger number of lower risk gene variants probably interacting together [1]. Model-based linkage analysis in multiple-case families, followed by positional cloning, led to the identification of BRCA1 and BRCA2. The cancer risks conferred by mutations in these genes are now well established, but together they explain only approximately 25% of the overall excess familial risk. Families with at least four cases of breast cancer and at least one case of ovarian cancer can be attributed largely to BRCA1. Multiple-case families with at least one case of male breast cancer are mainly due to BRCA2. But the majority of families with four or five cases of female breast cancer diagnosed before the age of 60 are not due to BRCA1 or BRCA2. This has been taken as evidence that one or more moderate-risk to high-risk breast cancer susceptibility genes still remain to be identified [2]. …