Androgen receptor: CAG repeat length and transcriptional levels related to prostate cancer

ABSTRACT

Objectives: The present work evaluates variations of polymorphic [CAG]n repeats present at exon 1 of the AR gene, as well as relative levels of its transcript, in order to investigate associations of these factors with prostatic tumor genesis in the Brazilian male population. Methods: Genomic DNA was extracted from blood samples from patients with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and from a group of young Brazilian males to determine the number of [CAG]n repeats amplified by PCR. Mutation analysis in this amplified fragment was carried out using the LIS-SSCP technique. Total RNA was extracted from prostatic tissue to evaluate the AR gene transcript levels using semi-quantitative multiplex RT-PCR. Results: CAG length varied from 14 to 30, with an average of 21 repeats for PCa and the male group and 20 for the BPH group. No significant difference was found for [CAG]n polymorphism among the analyzed groups and there was no sporadic change in the amplified portion of the AR gene, nor loss of [CAG]n repeats, demonstrating that these do not contribute to the cancer occurrence. Nevertheless, the positive association between short alleles and TNM pT3 staging may indicate that CAG repeats is associated to PCa progression. The transcriptional levels were significantly increased in PCa than in BPH and were associated with serum PSA levels of 5-10 ng/mL. As diagnostic clinical parameter, the levels of AR gene presented 17-fold higher chance for PCa occurrence, 60% of sensibility and 95% of specificity. Conclusion: The data suggest that the highly miscegenated Brazilian male population presents a high frequency of [CAG]n short repeats, which may be associated with the PCa progression, while AR mRNA levels seems to be a good indicator of the incidence of this pathology, being useful in clinical practice for distinguishing patients with PCa from those with BPH.