Lack of association between androgen receptor CAG polymorphism and familial breast/ovarian cancer

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat in exon 1 that is inversely correlated with AR transcriptional activity in vitro. Several studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer. More recently, AR allele length was also inversely correlated with the histological grade of breast cancer, but no association was found between the AR-CAG polymorphism and the risk of either breast or ovary cancer. On the contrary, it was proposed that a longer CAG repeat sequence might be associated with an increased risk of breast cancer in BRCA1 mutation carriers, thus suggesting a different role of the AR-CAG polymorphism in sporadic and inherited breast cancers. With the intent of better understanding the role of the AR-CAG polymorphism as a cancer risk modifier, we defined the AR genotype of 151 patients (101 with breast and 50 with ovary cancer) belonging to high-risk breast/ovary cancer families. No difference in CAG repeat length was found between either breast and ovary cancer patients or age at diagnosis of both tumors. These results were also confirmed in a sub-group of 47 breast cancer cases, that either carried a BRCA gene mutation (11 cases) or were identified by very stringent operational criteria as hereditary breast cancers. Even though a substantially larger sample size would be required to reach conclusive evidence, our findings suggest that the AR-CAG polymorphism does not act as a modifier of tumor onset or tumor phenotype in breast/ovarian cancer families.