Association of androgen receptor, prostate-specific antigen, and CYP19 gene polymorphisms with prostate carcinoma and benign prostatic hyperplasia in a north Indian population.
The genes involved in androgen pathway and metabolism have been reported to contribute considerably to prostate carcinoma (CaP) risk. The present study investigated the association of androgen receptor (AR), prostate-specific antigen (PSA or KLK3), and cytochrome P450 (CYP19) gene polymorphisms in CaP (n=105) and benign prostatic hyperplasia (BPH) (n=120) in comparison to normal healthy controls (n=106) in an Indian population. We also evaluated the functional consequences of these gene variants on AR and PSA mRNA expression. Significant association of short AR CAG repeats (≤24) with risk of CaP (odds ratios [OR]=2.98, p<0.001) and BPH (OR=1.96, p=0.01) was observed; however, CYP19 gene polymorphism was not found to be associated with disease phenotype (p>0.05). PSA G-158A SNP was found to be significantly associated with risk of CaP (AA: OR=2.68, p=0.016 and GA: OR=2.07, p=0.018) p-trend 0.031 and BPH (AA: OR=3.46, p<0.001 and GA: OR=2.47, p=0.03) p-trend 0.009, respectively. PSA G-158A genotype independently increased the risk of developing BPH (OR=16.37, p<0.001), irrespective of AR CAG repeat length. Using quantitative real-time polymerase chain reaction, we found a significant upregulation of AR and PSA mRNA expression in CaP comparison to BPH. While short AR CAG (≤24) repeats were associated with higher AR mRNA expression in CaP (p=0.002), the PSA SNP did not correlate with its mRNA expression. Interestingly, significantly higher risk estimates for CaP were observed for the combined analysis of short AR CAG and CYP19 genotypes (A2A2) (OR=7.18, p<0.001) or A2A3 (OR=7.60, p=0.004). Our results suggest significant association of androgen signaling gene polymorphisms with risk of CaP and BPH and provide evidence for a putative functional role of AR CAG repeat in regulating its mRNA expression and warrant the need of larger studies in the Indian population to confirm our results.
National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
Abha
A
Soni
Anju
A
Bansal
Ashwani Kumar
AK
Mishra
Jyotsna
J
Batra
Laishram Chandreshwor
LC
Singh
Anurupa
A
Chakraborty
Dhirendra Singh
DS
Yadav
Nayan K
NK
Mohanty
Sunita
S
Saxena
D000368:Aged; D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011470:Prostatic Hyperplasia / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*
D012333:RNA, Messenger; D011944:Receptors, Androgen; D001141:Aromatase; D017430:Prostate-Specific Antigen