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.
We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases.
To evaluate the potential contribution of mutations in the BRCA1 and BRCA2 genes to male breast cancer (MBC), we expanded a previous study to screen a total of 261 Israeli men diagnosed with breast carcinoma.
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.
Several susceptibility genes have been established for female breast cancer, of which mutations in BRCA1 and especially in BRCA2 are also known risk factors for male breast cancer (MBC).
Pathogenic variants in BRCA2 [odds ratio (OR) = 13.9; p = 1.92 × 10<sup>-16</sup>], CHEK2 (OR = 3.7; p = 6.24 × 10<sup>-24</sup>), and PALB2 (OR = 6.6, p = 0.01) were associated with significantly increased risks of MBC.
Forty one male breast cancer samples were studied, including one sample from a man with spinal and bulbar muscular atrophy (SBMA), which is caused by an AR CAG repeat expansion.
However, the clustering of early pancreatic cancer in families with two breast cancers under age 50 years, the aggregation of ovarian cancer in families with breast and ovarian cancers, and the increased incidence of early onset prostate cancer in families with male breast cancer seem to be due to other effects unrelated to BRCA1/2 mutations.
Heterozygous germ line mutations in the Breast CAncer1 (BRCA1) and BRCA2 genes can lead to a high risk of breast and ovarian cancer, in addition to a significantly increased susceptibility of pancreatic, prostate and male breast cancer.
Arg607-Gln and Arg608-Lys point mutations in the DNA-binding domain of the AR gene have been associated with male breast cancer in partial androgen insensitivity syndrome.
Two heritable gene defects have been associated with a predisposition to male breast cancer development, ie., germ-line mutations in the breast cancer susceptibility gene BRCA2 and the androgen receptor (AR) gene.