The proportion of older-onset breast cancer attributable to BRCA 1 is not yet determinable, because both inherited and sporadic cases occur in older-onset families.
One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail.
A comparison of the Cancer and Steroid Hormone Study (CASH) model and a model which assumes a rare dominant susceptibility locus with low penetrance and no phenocopies stresses the difficulties in assessing linkage if the assumptions of the CASH model in terms of age at onset of breast cancer are not appropriate for the BRCA1 locus.
Women with germline mutations in BRCA1 are estimated to have an 85% lifetime risk of developing breast cancer and an increased but as yet undetermined risk of ovarian cancer.
The imminent isolation of BRCA1 will make predictive testing for breast cancer a reality for many women and likely will pave the way for novel diagnostic and therapeutic strategies in the future.
The identification and cloning of the BRCA1 gene is imminent, and will facilitate the screening and counselling of families at risk of breast cancer, and in the longer term may open up new therapeutic possibilities.
In addition, many of the markers reveal genetic polymorphisms and may be tested in breast cancer families and in loss-of-heterozygosity studies of sporadic breast cancers to better define the BRCA1 gene candidate region.
We provide genetic evidence supporting the identity of the candidate gene for BRCA1 through the characterization of germline mutations in 63 breast cancer patients and 10 ovarian cancer patients in ten families with cancer linked to chromosome 17q21.
Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor.
Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.
A gene from chromosome region 17q12-q21, designated BRCA1, identified in 1990 by Dr Mary-Claire King and colleagues, predisposes to both cancer of the breast and the ovary.
The recent identification of the BRCA1 gene in early-onset hereditary site-specific breast cancer and the HBOC syndrome has led to new challenges for the genetic counselor.
A breast-ovarian cancer susceptibility gene, BRCA1, which is responsible for disease in approximately 45% of breast cancer families and most families that contain breast and ovarian cancer, has been assigned by genetic linkage to 17q12-21.
We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer.
In a study of nine families with "site-specific" ovarian cancer (criterion: three or more cases of epithelial ovarian cancer and no cases of breast cancer diagnosed at age < 50 years) we have obtained evidence of linkage to the breast-ovarian cancer susceptibility gene, BRCA1 on 17q12-21.
The survival curve of patients with breast cancer was less steep in BRCA1 gene carriers than that in the general population; 5-, 10- and 20-year survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent respectively.