We hypothesize short AR allelotypes promote aggressive ovarian cancer phenotype through modulation of epidermal growth factor receptor (EGFR) signaling.
Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) ovarian cancer and control subjects without a personal or family history of cancer (n = 50).
We analyzed CAG and GGC repeat length polymorphisms in the AR gene using data from a population-based case-control study of ovarian cancer that included 594 cases and 681 controls.
Similar results have been obtained in prostate (regulation of enzymes involved in androgen synthesis and modulation of androgen receptor levels and activity) and ovary cancer.
Anti-androgen use early in the course of ovarian cancer is more likely to be effective as these data suggest that androgen receptor expression decreases with exposure to chemotherapy and this may explain the low response rates seen in clinical trials of patients heavily pre-treated with multiple courses of chemotherapy.
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.