Genetic recombination between IGFBP4 and BRCA1 places IGFBP4 centromeric to the cancer susceptibility gene and effectively excludes it as a candidate gene for BRCA1.
In addition, increased transcription of mammary Brca1 during pregnancy might contribute, in part, to the reduced cancer risk associated with exposure to pregnancy and lactation.
The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown.
We describe a 43-year-old woman from a hereditary breast-ovarian cancer (HBOC) family which showed linkage to BRCA1 and who was at inordinately high risk for cancer but who was denied insurance coverage for prophylactic oophorectomy, despite strong recommendations by her gynecologist and a cancer geneticist-medical oncologist.
A genetic recombinant in a breast-ovarian cancer family indicates a placement of BRCA1 telomeric to D17S776, and helps to define the region of assignment of the cancer susceptibility gene.
If the risk of cancer in these families is assumed to be restricted to the ovary, the best estimate of the proportion of families linked to BRCA1 is .78 (95% confidence interval .32-1.0).
Markers from this map can be used to determine whether cancer is linked to BRCA1 in families, to evaluate whether tumors have lost heterozygosity at loci in the region, and to identify probes for characterizing chromosomal rearrangements from patients and from tumors.
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.
We sought BRCA1 mutations in women who were given a diagnosis of breast cancer at an early age, because early onset is characteristic of a genetic predisposition to cancer.
To establish whether known risk factors modify susceptibility to cancer in these women, we have studied the reproductive histories of 333 North American women who were found by haplotype analysis to carry BRCA1 mutations.
Differences in cancer risk profiles observed in these families with multiple ovarian cancer and in carriers of the gene BRCA1 suggest that hereditary ovarian cancer is genetically heterogeneous.
The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development.
BRCA1 mutations were identified in nine of 29 (approximately 31%) patients with a family history of cancer and in three of 41 (approximately 7%) women with early-onset breast carcinomas, and were subsequently characterized by sequence analysis.
With the ability to identify inherited mutations in BRCA1, prophylactic oophorectomy and other interventions intended to decrease cancer mortality can be offered specifically to women who carry a mutation, but the optimal strategy for decreasing cancer mortality in BRCA1 families has not yet been determined.
Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1185delAG mutation.
A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that pancreatic adenocarcinoma can be a feature of cancer susceptibility syndromes associated with germline mutations in p16, BRCA1, BRCA2, and APC.
In all three cases, there is a strong family history of breast, ovarian, or other cancers possibly related to a BRCA1 defect and family members showed a high concordance of cancer incidence with the presence of R841W.
Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up.
Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2."