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.
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.
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.
In addition, if acquired genetic mutations of the BRCA1 gene are involved as early events in the development of non-familial forms of the disease, early detection of possible breast carcinoma may become feasible in biopsy of breast tissue.
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.
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.
One such gene (p53) has been identified and a second (BRCA1) has been precisely mapped in the human genome, but further breast cancer predisposition genes remain to be identified.
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 breast cancer susceptibility gene BRCA1 has been cloned and a second susceptibility gene, BRCA2, chromosomally mapped; will most breast and ovarian cancer turn out to be familial?
Since the proportion of families linked to BRCA1 is larger in Western early-onset breast cancer families than in late-onset ones, we also summed the LOD scores of five early-onset families.
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.
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.
Our results indicate that there is a gene(s) other than BRCA1 which predisposes to early-onset breast cancer in women and which confers a higher risk of male breast cancer.