South Indian men with reduced CAG repeat length in the androgen receptor gene have an increased risk of prostate cancer

Abstract

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.

Evaluation of the effects of androgen receptor gene trinucleotide repeats and prostate-specific antigen gene polymorphisms on prostate cancer

“…Shorter CAG repeats have been associated with prostate cancer risk as well as an aggressive form of the disease. The relationship between the length of GGC repeats and prostate cancer risk, however, is not clearly understood (Irvine et al, 1995;Zeegers et al, 2004;Mishra et al, 2005;Krishnaswamy et al, 2006).…”

“…However, transcriptional activity may increase when repeats are high. Therefore, shorter repeats may comprise higher risk for prostate cancer (Irvine et al, 1995;Zeegers et al, 2004;Mishra et al, 2005;Krishnaswamy et al, 2006;Rodríguez-González et al, 2009).…”

“…The effect of the variation in the length of the GGC tract on AR activity is unclear, but it has been thought that the GGC trinucleotide repeats range from 10 to 30 the transcriptional activity of the AR gene (Gao et al, 1996;Zeegers et al, 2004;Mishra et al, 2005;Krishnaswamy et al, 2006). However, to date, no relationship has been established between the length of the polyglycine region and infertility (Tut et al, 1997).…”

GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene and prostate cancer risk in south Indian men

“…In vitro investigations suggest that CAG repeat length correlate inversely with AR transactivation (Chamberlain et al 1994). The longer CAG repeat length found to be associated with male infertility (Patrizio et al 2001), while the short CAG repeat length of the AR has been reported to predispose to prostate cancer (Coetzee et al 1994;Mishra et al 2005;Krishnaswamy et al 2006). However, the effect of the variation in the length of the GGN tract on AR activity is unclear.…”

“…In India, a significant association has been identified between short CAG repeats and prostate cancer risk in North Indian men (Mishra et al 2005), as well as our earlier study on the South Indian men (Krishnaswamy et al 2006). This raised curiosity to determine the role of GGN repeat polymorphisms and its linkage with CAG repeats in prostate cancer risk in South Indian men.…”