[New polymorphisms in the PSA promoter in patients with prostate carcinoma].
BACKGROUND
PSA is still the most important parameter in the diagnosis and follow-up of prostate cancer. We searched for single nucleotide polymorphisms (SNP) in four different parts of the PSA promoter, which harbour binding sites for major transcriptional regulators using PCR-based combined SSCP and sequence analysis.


METHODS
Lymphocyte DNA samples from 279 prostate cancer patients and 55 age-matched controls were subjected to SSCP analysis after PCR amplification of four approximately 200-bp fragments selected to contain the known AREs I-III or the transcriptional start site, respectively. Conspicuous PCR fragments with variant SSCP patterns were subsequently cloned and sequenced. Computer-assisted comparison with published sequences of the promoter region was performed to reveal polymorphic sites.


RESULTS
In 66.6 % of the carcinoma cases DNA displayed polymorphisms in ARE I-, whereas the benign cases showed this SNP only in 14.5 %. This difference was highly significant (p < 0.0001). In addition, we found novel SNPs with lower frequency at positions - 179, - 230, - 233 (ARE I) and - 356 (ARE II).


CONCLUSIONS
The present study confirmed that the otherwise already described polymorphism in the position - 158 is highly significantly more frequent in prostate cancer patients than in the control group. There is no significant correlation to the clinical stage of the disease. Furthermore we described for the first time four rare, previously unknown polymorphisms.
Schostak
M
M
Urologische Klinik und Hochschulambulanz der Charité - Universitätsmedizin Berlin. martin.schostak@charite.de
Braun
C
C
Krause
H
H
Miller
K
K
Kempkensteffen
C
C
Hinz
S
S
Strenziok
R
R
Blana
A
A
Schrader
M
M
D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D017430:Prostate-Specific Antigen