Increased frequency of long androgen receptor CAG repeats in male breast cancers

We have investigated the possible link between androgen hyposensitivity caused by long androgen receptor (AR) CAG repeats, and breast carcinogenesis, in men. AR gene mutations have been described in men with androgen insensitivity syndrome and breast carcinoma, and some studies have shown long CAG repeats are associated with increased risk of breast cancer in women. DNA was isolated from male breast cancer biopsies, and the AR CAG repeat sized. 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. The man with breast cancer and SBMA had 49 CAG repeats (normal range 6–35), but all other breast cancer samples had repeats within the normal range. The frequency of CAG repeats ≥24 was significantly higher in the breast cancer group (excluding the SBMA subject) than in the normal population (p<0.05), and was more marked in grade I and II tumors (p=0.001). There was no correlation between AR CAG repeat length and age at diagnosis. In conclusion, longer AR CAG repeats are more common in men with breast cancer than in the control male population. Androgen hyposensitivity, caused by long AR CAG repeats, may increase the risk of breast cancer in men.