Androgen Receptor CAG Repeat Length and Association With Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

Abstract

PURPOSE We investigated the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the androgen receptor (AR) gene and the risk of prostate cancer. METHODS This is a nested case-control study of 1159 cases and 1353 controls drawn from the Prostate Cancer Prevention Trial, a randomized, placebo-controlled trial testing whether finasteride, a 5α-reductase inhibitor, could reduce the 7-year period prevalence of prostate cancer. During the course of the PCPT, men underwent annual DRE and PSA measures and a prostate biopsy was recommended for all men with an abnormal DRE or a finasteride-adjusted PSA of > 4.0 ng/mL. Cases were drawn from men with biopsy-determined prostate cancer identified either by a for-cause or end-of-study biopsy and controls were selected from men who completed the end-of-study biopsy procedure. RESULTS CAG repeat mean lengths were not different between cases and controls. The frequency distribution for cases and controls for the AR CAG repeat length is similar. There were no significant associations of CAG repeat length with prostate cancer risk, either when stratified by treatment arm (finasteride or placebo) or when combined together. There was also no significant association between CAG repeat length and the risk of low- or high-grade prostate cancer. CONCLUSIONS There were no associations of the AR CAG repeat length and prostate cancer risk. Knowledge of AR CAG repeat length provides no clinical useful information for predicting prostate cancer risk.

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

“…In our cohort of Bulgarian patients and controls the length of the repeats ranged between 14 and 29 to 31, with a peak at 21 repeats and another at 24 repeats ( Figure 2). Our results for CAG repeat polymorphism in AR (Tables 6 and 8) are consistent with some recent studies that did not find any association of this microsatellite with either PC risk (20,21) or with time to progression, overall survival, Gleason score, and clinical stage at diagnosis (22). Conflicting conclusions may be due to differences in design, small sample size in some studies, differences in environment, genetic admixture, ascertainment bias (including diagnosis before or after the age of PSA testing), and differences in tract length cut off points.…”

Androgens and androgen receptor signaling in prostate tumorigenesis

“…One suggestion that AR plays a causative role in tumorigenesis comes from studies demonstrating an association between CAG repeat length, which influences AR activity, and the risk of prostate cancer (PC); however, other studies contradict these findings (Bosland 2000, Nelson et al 2003, Lindstrom et al 2010, Price et al 2010. Two studies of genetically modified mice suggest that AR plays a role in cancer initiation.…”

Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy

“…Epidemiological studies initially found association between fewer CAG repeats and increased risk or more aggressive disease (e.g., (Irvine et al, 1995;Giovannucci et al, 1997;Stanford et al, 1997)). However results vary with ethnic group and most recent studies find no association with risk (e.g., (Lindstrom et al, 2010;Price et al, 2010)). Conflicting conclusions stem from many aspects of study design, including small sample sizes, differences in environment, genetic admixture, ascertainment bias (including diagnosis before or after the age of PSA testing) and differences in tract length cut-off points.…”