The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy.

Abstract

The authors examined the impact of the number of CAG repeats in exon 1 of the androgen receptor on disease progression among men with prostate carcinoma after prostatectomy. This polymorphism has been associated with alterations in activity of the androgen receptor in in vitro systems and with the risk of clinically diagnosed prostate carcinoma in some epidemiologic studies. An earlier series found that, among men at low risk of progressive disease, a small number of CAG repeats predicted a high risk of recurrence, and the impact of CAG repeats varied among men with different risks of progressive disease. The authors analyzed specimens from a large clinical series of fixed tissue specimens from men who underwent prostatectomy at a single institution, including 413 American white men (WM) and 298 African-American men (AAM), with 5-10 years of available clinical follow-up. There was little association between the number of CAG repeats and extent of disease, Gleason score, and preoperative PSA level at diagnosis. Overall, patients who had > 18 CAG repeats had a greater risk of recurrence compared with patients who had </= 18 CAG repeats (hazard ratio [HR] = 1.52; P = 0.03). Excess risk was not found among men who were at low risk of recurrence (HR = 0.93; P = 0.96); however, among men who were at high risk of recurrence, the risk elevated for WM (HR = 1.75; P = 0.28), AAM (HR = 1.49; P = 0.06), and both races combined (HR = 1.53; P = 0.03). Overall, men with prostate carcinoma who had > 18 CAG repeats had an estimated 52% increased risk of disease recurrence. The increased risk could be attributed to men who were at high risk of recurrence.