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.
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?
Our results suggest that the majority of breast cancer families with less than four cases and no ovarian cancer are not due to rare highly penetrant genes such as BRCA1 but are more likely to be due either to chance or to more common genes of lower penetrance.
In the context of high-risk families the most important genes are BRCA1 on chromosome 17q, which is associated with a high penetrance of both breast and ovarian cancer, and BRCA2 on chromosome 13q, which causes a high risk of breast cancer but a lower risk of ovarian cancer.
We have studied BRCA1, the breast cancer susceptibility gene, as a determinant of susceptibility to breast cancer by linkage analyses in 11 families, but our results indicate that BRCA1 may not be important for development of familial breast cancer in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)
The development and refinement of risk prediction models provide an epidemiologic basis for counseling women with a family history that does not appear related to a dominant susceptibility gene. contrast, the recent isolation of BRCA1, the localization of BRCA2, and the acknowledgement that additional breast cancer susceptibility genes must exist provide a molecular basis for counseling some high-risk women.
Four hundred eighty-four patients undergoing mammography and 498 patients visiting their obstetrician-gynecologist were asked whether they would take a breast cancer 1 (BRCA1) test to detect a genetic susceptibility to breast cancer.
We have studied 28 breast and 6 ovarian tumors from families with strong evidence for linkage between breast cancer and genetic markers flanking BRCA1.
However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations.
Thus, the proportion of families who inherit the mutated BRCA1 allele seems to be small among Japanese breast cancer families and Japanese breast-ovarian cancer families.
However, there is significant evidence of heterogeneity of risk between families; a much better fit to the data is obtained by assuming two BRCA1 alleles, one conferring a breast cancer risk of 62% and an ovarian cancer risk of 11% by age 60 years, the other conferring a breast cancer risk of 39% and an ovarian cancer risk of 42%, with the first allele representing 71% of all mutations (95% CI 55%-87%).
Recently, linkage analyses of large families with a predisposition to breast cancer have been performed in order to map breast cancer susceptibility genes (TP53, BRCA1, BRCA2).
The extracted DNA was typed by polymerase chain reaction amplification and the derived haplotypes submitted to linkage analysis which confirmed that in 12 families breast cancer susceptibility could be traced to BRCA1.
The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility.
Because high rates of breast cancer are associated with loss of BRCA1 in humans, it is possible that this gene provides an important growth regulatory function in mammary epithelial cells.
These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression.
We conclude that the analysis of BRCA1 gene expression by mRNA in situ hybridization may be useful in screening for patients with BRCA1-linked 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.
The isolation of the breast and ovarian cancer gene 1 (BRCA1) has brought about the potential for screening large numbers of individuals for genetically increased susceptibility to breast cancer.