Identification and Genetic Mapping of Genes for Hereditary Breast and Ovarian Cancer in Families Linked to BRCA1

摘要

In pursuing our aims to characterize BRCA2, we continue to screen for BRCA2 mutations in 40 high-risk breast cancer families. With 85% of the coding sequence examined, we have identified one missense mutation and several polymorphisms. A search for large deletions and/or rearrangements in BRCA2 in 10 families detected no variants. We are now performing long-range PCR across the gene to confirm those results. In characterizing BRCA2, we found no difference in prognosis between mutation carriers and breast cancer patients with no known mutations, even though the carriers have worse prognostic indicators than the controls. A second study found that oral contraceptive use reduced ovarian cancer risk by 50% in BRCAl and BRCA2 mutation carriers. A study of recurring BRCA2 mutations, determined that they likely were founder mutations as there was no evidence for multiple origins for identical mutations. Our results were also consistent with previous reports of an ovarian cancer cluster region in BRCA2, and in this region, breast cancer cases had a significantly older mean age at diagnosis than seen outside the region. An examination of the role of the founder I1307K APC mutation on occurrence of breast cancer in Ashkenazi Jewish women found the association largely limited to those with either a BRCAl or BRCA2 mutation.