Similarly, in the two cases of male breast cancer in which AR gene mutations have been described, the mutations in the DNA binding domain of the receptor are alike.
The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations.
The recently discovered BRCA2 gene on chromosome 13q is thought to account for some families with increased risk of breast cancer, including male breast cancer.
None of the 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1.
Moreover, androgen receptor gene alterations have been recently described in two unrelated diseases: male breast cancer and spinal and bulbar muscular atrophy.
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.
This androgen receptor mutation along with the Arg608 into Lys mutation we describe, suggests that this genetic abnormality is not fortuitous: a decrease in androgen action within the breast cells could account for the development of male breast cancer by the loss of a protective effect of androgens on these cells.
BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer.
We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer.
The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families.
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.
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.
Germline mutations of BRCA2 are predicted to account for approximately 35% of families with multiple case, early onset female breast cancer, and they are also associated with an increased risk of male breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.
The remaining eight cases (89%) of male breast cancer with a family history of breast/ovarian cancer in first-degree relatives remain unaccounted for by mutations in either the BRCA1 gene or the BRCA2 gene.
We have adjusted the model to include BRCA2, but the use of this version must await publication of penetrance data for BRCA2, including those for male breast cancer that are apparently associated with BRCA2 but not with BRCA1.
We have adjusted the model to include BRCA2, but the use of this version must await publication of penetrance data for BRCA2, including those for male breast cancer that are apparently associated with BRCA2 but not with BRCA1.
Germline mutations of BRCA1 are also associated with ovarian cancer and mutations of BRCA2 are associated with an increased risk of male breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.