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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Schatzl
Georg
G
Department of Urology, Medical University of Vienna, Vienna, Austria. georg.schatzl@meduniwien.ac.at
Marberger
Michael
M
Remzi
Mesut
M
Grösser
Petra
P
Unterlechner
Julia
J
Haidinger
Gerald
G
Zidek
Thomas
T
Preyer
Martin
M
Micksche
Michael
M
Gsur
Andrea
A
D000328:Adult; D000368:Aged; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics*; D013739:Testosterone / Q000097:blood*
D011944:Receptors, Androgen; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017430:Prostate-Specific Antigen