The androgen receptor (AR) gene possesses polymorphic CAG tandem repeats and the repeat length has been inversely related to the risk of prostate cancer (PCa). The distinct ethnic variation in the CAG repeat length may be correlated to differences in PCa risk in different populations. To evaluate the CAG repeat length in the AR gene and the implications for PCa, we screened 87 PCa patients and 120 control subjects from South India. The mean CAG repeat length in PCa patients was significantly smaller than that of controls (17.0 vs 20.7; P<0.001). Men with £ 19 CAG repeats had a significantly increased risk of cancer compared to those with >19 CAG repeats (age-adjusted OR=7.01; 95% CI=3.52-13.94; P<0.001). However, no significant association was observed between CAG repeats and age of onset or prostate-specific antigen levels. Although there was a trend towards shorter CAG repeat length in high grades of cancer, it was not significant (P=0.085). Thus, our results suggest an association between short CAG repeats in the AR gene and PCa risk in South Indian men. Further, we propose that CAG repeats could be used as a prognostic marker for PCa diagnosis.

The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a casecontrol study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats £21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52-1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG £19/GGN £21 (OR-5.2 at 95% CI-2.17-12.48, P < 0.001) and CAG £19/GGN > 21(OR-6.9 at 95%CI-2.85-17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG £19/GGN £21 and CAG £19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men.

Testosterone is converted to 5 a-dihydrotestosterone (DHT) by 5 a-reductase enzyme, which is encoded by the SRD5A2 gene. DHT is the main androgen responsible for prostate growth. We have analyzed the complete coding region of the SRD5A2 gene in 87 histologically confirmed prostate cancer (PC) patients, 40 benign prostatic hyperplasia (BPH) cases, and 96 control samples from southern parts of India. The study revealed the A49T site to be monomorphic, the V89L site to be highly polymorphic, and the (TA) n repeat site to be polymorphic with only 2 alleles in our populations. The distribution of V89L alleles between PC cases and controls was not significantly different; however, (TA) 9 alleles distributed differently between the 2 groups. BPH cases exhibited alleles similar to controls at all polymorphic sites. The sequencing of the whole coding region did not reveal any other known or novel polymorphism in this gene. Our study emphasizes that the (TA) 9 allele might confer certain PC risk but that A49T and V89L polymorphisms do not confer PC risk in South Indian men.