The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation BRCA2 together may account for over a quarter of all early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.
We used linkage and haplotype analysis with simple tandem repeat polymorphisms at chromosomal bands 17q21 and 13q12 to determine the contribution of the BRCA1 and BRCA2 genes to predisposition to breast cancer in four Australian breast cancer kindreds, one of which had two male cousins with breast cancer.
Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.
We describe the proportion of hereditary breast cancer explained by BRCA1 or BRCA2 in a sample of North American hereditary breast cancers and assess the evidence for additional susceptibility genes that may confer hereditary breast or ovarian cancer risk.
Recent studies have identified mutations in the breast and (ovarian cancer susceptibility gene 2 (BRCA2), one which has been found in the germline of several males and one female affected with breast cancer.
BRCA2 carries a risk of breast cancer similar to that of BRCA1, but is associated with a lower risk of ovarian cancer and a higher risk of male breast cancer.
Loss of heterozygosity studies at the retinoblastoma and breast cancer susceptibility (BRCA2) loci in pituitary, parathyroid, pancreatic and carcinoid tumours.
The steady state levels of BRCA1 and BRCA2 mRNAs were shown to be coordinately elevated by the steroid hormone estrogen but not progesterone in the human breast cancer cell lines BT-483 and MCF-7.
We have analyzed the expression of the breast cancer susceptibility gene, Brca2, in mammary epithelial cells as a function of proliferation and differentiation.
Loss of heterozygosity (LOH) was analysed in 84 primary tumours from sporadic, familial and hereditary breast cancer using five microsatellite markers spanning the chromosomal region 13q12-q13 which harbours the BRCA2breast cancer susceptibility gene, and using one other marker located within the RBI tumour-suppressor gene at 13q14.
Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2.
Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations.
BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops.
Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer.