The Association of CAG Trinucleotide Repeats of Androgen Receptor Gene with the Incidence of Castrate Resistant Prostate Cancer in Javanese Population

Abstract

Androgens play an important role for prostate cells proliferation, survival and development of prostate cancer (PCa). Androgen ablation therapy is a common procedure to treat PCa. However, in most of the cases PCa relapse after 18-24 months of therapy and develop into castration resistant prostate cancer (CRPC). Polymorphism in Androgen Receptor (AR) gene has been known as a risk factor for PCa and CRPC. This study aims to evaluate the association of the length of CAG repeats within AR with the incidence of CRPC in Javanese population, in Indonesia. Forty two patients enrolled in this study, genomic DNA was extracted from peripheral blood leukocytes, PCR was performed to amplify exon 1 of AR and genotyping of CAG repeats was performed by Sanger Sequencing. Of the 42 patients, 17 were excluded from the study due to incomplete data after 9 months of observation. Of the 25 remaining patients, three of them (12%) experienced tumor-relapse and developed CRPC phenotype after hormonal therapy. The mean of PSA levels were 277.5 and 240.7 mg/dL for CRPC patients and non-CRP patients respectively (p =0.886). We observed that the CRPC patients tend to have shorter CAG repeats (22) than those of non-CPR patients (24) (p=0.878). Whereas the mean of Gleason score of CRPC patients (7) were slightly higher than those of non-CRP patients (6,3) (p=0.859). Although not significant, Kaplan Meier curve analysis showed that the CAG repeats lower than 22 repeats had a better survival compared to those who have CAG repeats longer than 22. In conclusion, there was no significant association between the lengths of CAG repeats with the incidence of CRPC in Javanese population, however we observed that CRPC patients tend to have shorter length of CAG repeats, lower Gleason score and higher PSA levels pre-ADT (androgen deprivation therapy) compared to those of non-CRP patients.