Role of an Androgen Receptor Gene Polymorphism in Development of Hormone Refractory Prostate Cancer in an Indian Population


Background: Androgen receptors play critical roles in the development of primary as well as advancedhormone-refractory prostate cancers. Since the growth of prostate cancer is androgen-sensitive, metastatic diseasehas been treated by hormonal therapy in the form of androgen ablation. Prostate cancer cells rely on androgenreceptor (AR) for proliferation and survival. Aim: To evaluate the prognostic significance of androgen receptorpolymorphism in patients under hormonal therapy in any form.
Methods: Complete follow up data were availablefor 87 patients out of 130 patients enrolled for study. DNA was extracted from blood samples using salting outmethod and then subjected to PCR Genscan for CAG and GGN genotyping. The mean follow up was 10.12±8.83months.
Results: Out of 87 patients, 64 experienced clinical as well as biochemical recurrence. The overallhormone refractory rates were 73.4% after one year. We observed a significant shorter median CAG repeats inHRPC patients (20 vs 22). The hazard ratio for HRPCs with the ≤20 CAG repeat genotype was 0.602 (0.33-1.08,p=0.09). Kaplan-Meier analysis showed that HRPC rates were not significantly associated with CAG repeat(p=0.06) but a trend was observed with short CAG repeats. No significant association was observed with ARGGNrepeats.
Conclusions: A trend for association of AR-CAG repeats with HRPC patients in north Indianpopulation was observed, suggesting this to be a prognostic factor for determining the therapeutic regimen.