Novel polymorphisms in prostate specific antigen gene and its association with prostate cancer.
Prostate-specific antigen (PSA) is now used widely for the diagnosis and monitoring of patients with prostate cancer. The PSA gene is a target of the androgen receptor (AR) which interacts with androgen response elements (AREs) in the PSA gene promoter. Recently, we identified two novel polymorphisms in the PSA promoter ARE2 region in breast cancer. We hypothesized that some genetic variations might also exist in the AREs of prostate cancer, and that feature might correlate with cancer development and/or progression. To test this hypothesis, three AREs of the PSA gene promoter were characterized for 47 prostate cancer cases and 105 controls from the Japanese population. We demonstrated the presence of two polymorphisms at positions -252 (G or A) and -205 (A or AA), which were the same as those we have found in breast cancer. Interestingly, the -252 A was linked with the presence of -205 AA, and the -252 G was always linked with the presence of -205 A. Therefore, only A-AA and G-A (-252--205) alleles were present in the Japanese population. The proportion of patients who were either heterozygotes or homozygotes for the A-AA allele was not significantly different from that observed among 105 individuals without cancer (p = 0.726). However, comparing with G-A allele homozygotes, prostate cancer patients carrying at least 1 A-AA alleles tended to exhibit high serum PSA levels (p = 0.0002), poor differentiation (p = 0.0149) and advanced clinical stage (p = 0.0077). These results suggest that the novel polymorphisms identified in the PSA gene promoter may affect transcriptional activity of the PSA gene, and an excess of PSA production may enhance rapid progression of prostate cancer.
Yang
Q
Q
Second Department of Pathology, Wakayama Medical College, 811-1 Kimiidera, Wakayama City 641-0012, Japan. yang-qf@mail.wakayama-med.ac.jp
Shan
L
L
Segawa
N
N
Nakamura
M
M
Nakamura
Y
Y
Mori
I
I
Sakurai
T
T
Kakudo
K
K
D000368:Aged; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020218:Response Elements
D017430:Prostate-Specific Antigen