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 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.
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.
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.
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)
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.
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.
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.
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.
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.
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.
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.
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%).
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.