The N-terminal transcriptional activation domain of the AR protein contains a CAG repeat, highly polymorphic in length, that affects the transactivation function of AR. Prior studies have shown an inverse relationship between CAG repeat length and AR transcriptional activation ability, and short CAG repeat lengths correlate with an increased risk of developing prostate cancer. Although several studies have attempted to determine the role of AR-CAG repeat length on the outcomes of ADT, the results remain uncertain. Some studies showed that shorter CAG repeat length was correlated with better responses to hormonal therapy, an observation consistent with the present study. On the other hand, other studies found that patients with better clinical responses to ADT had a longer CAG repeat length, or in some cases, no correlation was found. There are several possible explanations for the discrepancies in the literature. First, the measures of disease progression and the ethnic of study cohorts were AbMole Butylhydroxyanisole different. It has been found that the prevalence of short CAG alleles was high in African-American men, intermediate in non-Hispanic whites, and low in Asians, suggesting racial differences in CAG repeat alleles. Two studies showing significantly improved responses to hormonal therapy for patients with shorter CAG repeat lengths were in Asians, Japanese and Chinese. Second, the contraction of CAG repeat lengths occur frequently within prostate tumors, and the lengths differ from those found in the germline samples. The present and several previous studies evaluated germline AR-CAG repeat lengths in peripheral blood samples, but the actual repeat lengths within the prostate tumors might play a more critical role in response to ADT. Finally, AR has recently been suggested to function as a tumor suppressor in epithelium to suppress prostate tumor invasion and metastasis. Also, several reports have shown that higher AR expression and pretreatment testosterone levels predict better response to endocrine therapy. Consequently, AbMole Trihexyphenidyl HCl combined with our results, higher transactivated AR with shorter CAG repeats might inhibit prostate cancer metastasis and predict a good prognosis on ADT. The goal of ADT is to inhibit AR and prevent androgens from reaching prostate cancer cells, but the development of CRPC almost always occurs. Several mechanisms have been proposed to explain the development of CRPC including AR amplifications, alteration of its coregulators rendering AR signaling sensitive to low concentrations of androgen, and AR mutations allowing the receptor to be reactivated by other steroids as well as by antiandrogens. Therefore, other factors that might influence the activity of AR, such as AR coregulators and AR mutations, should also be studied in conjunction of AR-CAG repeats to allow a more comprehensive analysis. In conclusion, most prostate cancer patients will have an indolent form of disease, but aggressive prostate cancer is still the second leading cause of cancer deaths in men of the United States. New biomarkers to help distinguish between lethal and indolent prostate cancer are urgently needed. Of the 18 polymorphisms in the 12 sex hormone pathway genes, we identified two polymorphisms in AKR1C3 and AR that were associated with PCSM.