Polymorphism in ARE-I region of prostate-specific antigen gene associated with low serum testosterone level and high-grade prostate cancer

To examine the impact of polymorphism in the androgen-responsive element I region of the prostate-specific antigen (PSA) gene on the serum testosterone level and Gleason score in patients with newly diagnosed, untreated prostate cancer (PCa). High-grade PCa is associated with a low serum testosterone level, and the testosterone level has been negatively correlated with the expression of PSA. Endocrine factors (including testosterone, follicle-stimulating hormone, and luteotropic hormone), PSA level, prostate volume, and Gleason score were measured in 134 patients with untreated, biopsy-verified PCa. PSA polymorphism was determined by polymerase chain reaction-based methods using DNA from peripheral blood samples. Patients with the PSA G/G genotype had lower serum testosterone levels (3.5 ± 1.2 ng/mL) than those with the A/A genotype (4.3 ± 1.6 ng/mL) or the A/G genotype (4.4 ± 1.5 ng/mL). The PSA level in the A/A and A/G genotype groups were significantly lower than that in the G/G genotype group (18.2 ± 55.0 ng/mL versus 20.5 ± 27.6 ng/mL, P = 0.013). In a multiple logistic regression model, the odds ratio for the G/G polymorphism was significantly increased for Gleason score (odds ratio 2.4, 95% confidence interval 1.6 to 10.4; P = 0.02) and serum testosterone level (odds ratio 0.44, 95% confidence interval 0.36 to 0.94; P = 0.01) relative to genotypes A/A and A/G. Our results showed that the PSA G/G genotype is associated with a greater Gleason score and serum PSA level but lower serum testosterone level and could be considered a risk factor for a poor outcome of PCa.