Cag Repeat Number in the Androgen Receptor Gene and Prostate Cancer

Abstract

Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5′ end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.

Positive association of the androgen receptor CAG repeat length polymorphism with the risk of prostate cancer

“…Regarding South American countries, Brazil reported an average of 20.65 CAGs for a population of Caucasian and African descents (37). In another study, Madjunkova et al (38) reported a mean repeat length of 21.5 CAGs in patients with PC from Macedonia. In a study that examined adenocarcinomas, the number of CAG repeats ranged from 12 to 30 and averaged 20, which was similar to that in a healthy Brazilian population.…”

Trinucleotide repeat length in the first exon of the androgen receptor gene may be associated with prostate carcinogenesis and facilitate prediction of prostate cancer aggressiveness

“…10 Another confounding factor is a broad diversity of cut-off values of repeat number considered "optimal" for the prediction of PC in series published to date. 7,8,11 We chose the cut-off values identical with those in the study of Mononen et al 9 Furthermore, our study recognized a GGN repeat count of 19 or lower as predisposing to PC. This relationship was also confirmed by Zeegers et al 10 ; however, as with the (CAG) n region, there is no consensus on the number of GGN repeats most predictive for PC.…”

“…5,6 This phenomenon is believed to predefine the sensitivity of peripheral tissue to circulating androgen, possibly influencing the susceptibility to PC along with clinical and pathological characteristics of the tumor. [7][8][9] Introduction Prostate cancer (PC) is a major health problem among men in Western countries. The incidence of this tumor has been rising in most industrialized countries, including Poland, although in the United States, the number of new PC cases has declined slightly in recent years, 1,2 along with a similar trend in mortality.…”

Is Male Infertility a Natural Defense or Forerunner of Cancer?

“…The effects of androgens are mediated through the androgen receptor (AR), a nuclear transcription factor encoded by the AR gene. Mutation and polymorphism in androgen has been reported to precipitate either male infertility or prostate cancer [29,[38][39][40][41][42]. The differences in CAG and GGN tender repeats in androgen receptor polymorphism have been implicated in ethnical diversity observed in the risk factors of prostate cancer [29].…”