Significance of the Cag Repeat Polymorphism of the Androgen Receptor Gene in Prostate Cancer Progression

Abstract

The length of the CAG repeat polymorphism of the androgen receptor gene may be important for prostate cancer recurrence among patients who are otherwise at low risk for recurrence after radical prostatectomy. These findings have potential implications for patient selection for adjuvant treatment, and for the development of novel treatments.

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

“…A variable number of CAG repeats (CAGr) in exon 1 of the AR gene on the X-chromosome, which normally ranges between 9 and 35 [27,28] encodes for a variable number of glutamine residues in the aminoterminal domain of the receptor and is inversely associated with the transcriptional activity of testosterone target genes [29,30]. As clinical consequences, the number of CAGr was shown to be inversely associated with the risk of prostate cancer [27,28,31,32,33], benign prostatic hyperplasia [34,35], sperm production [36,37], bone density [38], endothelial function and HDL-cholesterol concentrations [39] as well as depression [40]. Furthermore, abnormal expansion of the CAGr length leads to Kennedy's disease, which is accompanied by morphological hypoandrogenic traits [41,42].…”

The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer

“…Among published literature, both 18 and 22 repeat units have been used as cutoff definitions for short CAG repeat length with which significant relationships have been found with risk of developing prostate cancer, earlier age of diagnosis, and cancer aggressiveness. 5,9,17 Thus, similar CAG repeat lengths cutoff points were used in this study.…”

“…In contrast, a number of studies have not found an association between CAG repeat length and overall risk of prostate cancer, age of diagnosis, or aggressiveness. 8,10,13,[15][16][17] This discrepancy in the significance of the CAG repeat length as a predictor for prostate cancer behaviour may reflect the limited number of studies and small patient numbers, differences in patient selection between studies, technical differences in evaluating the CAG length, or a combination of factors. Standard treatment in advanced prostate cancer involves ADT to halt tumour progression.…”

“…6,7 The clinical evidence to support this relationship, however, is inconclusive. [8][9][10][11][12][13][14][15][16][17] Suzuki et al 18 found that a shorter CAG repeat length predicted for a better response to endocrine therapy. In contrast, Bratt et al 10 reported that a long CAG repeat length predicted for a better response to hormone therapy.…”

Androgen receptor antigen density and S-phase fraction in prostate cancer: a pilot study

“…Men with prostate cancer, who were at a low risk for recurrence by conventional prognosticators, were found to have a relative risk of recurrence of 8.07 if they had 18 or less CAG repeats. 6 Several authors have reported on the role of AR expression as a prognostic marker for response to hormone therapy, time to tumor progression, and as an indicator of tumor aggressiveness. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] A review of the literature on clinical studies involving AR expression shows a wide variation in tissue sampling, methods used for estimation of AR expression and correlation of the data.…”