Further molecular characterization of the nature and function of the different BRCA1 mRNAs and proteins should increase our understanding of this gene in the etiology of human breast cancers.
We analyzed DNA samples from women enrolled in a population-based study of early-onset breast cancer to assess the spectrum and frequency of germ-line BRCA1 mutations in young women with breast cancer.
The majority of the physicians surveyed believed that current BRCA1 testing can detect a genetic predisposition to breast cancer accurately enough to be clinically useful (81%) and that a young woman with a family history of breast cancer not currently having regular mammography is likely to benefit from DNA testing because a positive result may motivate her to start mammography earlier (88%).
These results are consistent with data suggesting that certain groups of Jewish women have a higher than expected rate of mutation in the breast-cancer gene BRCA1.
This was attributed mainly to nuclear polymorphism (P < 0.0001), mitotic activity (P < 0.0001), and tubular differentiation (P = 0.0004), implying that BRCA1-associated BCs are highly proliferating tumors.
Recently, the BRCA1 gene, which is responsible for 45% of hereditary early-onset breast cancer and for the majority of co-inheritance of breast and ovarian cancer, has been cloned.
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.
Heterogenous point mutations in the BRCA1breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs.
Using single-strand conformation polymorphism (SSCP) analysis, we examined primary breast cancers for mutations in coding exons of BRCA1 in a panel of 103 patients, of whom all either represented early-onset cases (< 35 of age), were members of multiply-affected families, and/or had developed bilateral breast cancers.
These results, together with penetrance estimates from linked families, suggest that approximately one woman in 800 carries BRCAI, the susceptibility gene on chromosome 17q, and that this gene causes about 1% of all breast cancers.
Requests for results were more frequent for persons with health insurance (odds ration [OR], 3.74; 95% confidence interval [CI], 2.06-6.80); more first-degree relatives affected with breast cancer (OR, 1.59; 95% CI, 1.16-2.16); more knowledge about BRCA1 testing (OR, 1.85; 95% CI, 1.36-2.50); and indicating that test benefits are important (OR, 1.45; 95% CI, 1.13-1.86).
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.
Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene.
BRCA1 germline mutations were found in one out of two families with ovarian cancer, in five out of eight families with breast-ovarian cancer, and in two out of 11 families with breast cancer.
With respect to sequence conservation, two interesting outliers are the breast cancer (BRCAI) gene product and the testis-determining factor (SRY), both of which display among the lowest degrees of sequence identity.
Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients who either came from small families with as few as one affected first degree relative, or in patients who had no family history but had developed breast cancer under 40 years of age.
On the basis of linkage to chromosomes 17q or 13q and/or the presence of ovarian and male breast cancer, HBC families were classified as either "BRCA1-related" (26 families, 90 breast cancer pathology cases) or "Other" (26 families, 85 cases), in which most BRCA2 cases were likely to reside.
In addition, the BRCA1 mutation 185delAG, which is prevalent in the Ashkenazi Jewish population, was sought with an allele-specific polymerase-chain-reaction assay in 39 Jewish women among the 418 women who had breast cancer at or before the age of 40.
From psychological approach to oncology (psycho-oncology), it should be able to help identify factors that will increase breast cancer screening compliance (early breast cancer detection) and participation in genetic testing (BRCA 1 gene) for heritable breast cancer risk.