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.
Male BC is almost exclusively hormone receptor positive (+), including the androgen receptor (AR), and is associated with an increased prevalence of BRCA2 germline mutations, especially in men with increased risk for developing high-risk BC.
Moreover, androgen receptor gene alterations have been recently described in two unrelated diseases: male breast cancer and spinal and bulbar muscular atrophy.
The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia.
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.
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.
Here, we investigated the contribution of BRCA1, BRCA2 and CHEK2 alterations to MBC predisposition in Italy by analysing a large series of MBC cases, unselected for breast cancer family history and all negative for BRCA1/BRCA2 germ-line mutations.
We wanted to evaluate the significance of CHEK21100delC in predisposition to MBC by assessing its frequency in a population-based material of 114 Finnish MBC patients.
Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs--rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)--showed significant differences in ORs (p<0.05) between sexes.
By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43-2.05; p = 0.0001), rs3803662/TOX3 (OR = 1.59; 95 % CI: 1.32-1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05-1.50; p = 0.013).
In summary, we advise restricting BRCA1 MLPA screening to those subgroups that revealed LGRs and recommend BRCA2 MLPA screening only for families presenting with cooccurrence of female and male breast cancer.
Here, we investigated the contribution of BRCA1, BRCA2 and CHEK2 alterations to MBC predisposition in Italy by analysing a large series of MBC cases, unselected for breast cancer family history and all negative for BRCA1/BRCA2 germ-line mutations.
These BRCA2 families have early-onset breast cancer (mean and median age = 49 years), with four of the eight families including ovarian cancer but with no families including male breast cancer.
We conclude that the predominant Jewish germline mutations in BRCA1/BRCA2 contribute to male breast cancer in Israel, primarily in Ashkenazi individuals with a family history of cancer.