Linkage between polymorphisms in the prostate specific antigen ARE1 gene region, prostate cancer risk, and circulating tumor cells.
BACKGROUND
The prostate specific antigen (PSA) gene has a polymorphic androgen response element (ARE) sequence with two alleles, A and G. PSA A-allele carriers have higher serum PSA levels in healthy men (HM).


METHODS
We analysed DNA samples from 278 (556 alleles) unrelated individuals, 127 HM and 151 prostate cancer (PC) patients, for PSA ARE1 genotypes.


RESULTS
The analysis of the frequencies from the 556 alleles indicates a significant overrepresentation of A-allele in the PC group under the age of 67 compared with the HM group (63.3% vs. 48.8%; P = 0.009). We found that men carrying two A-alleles have increased risk for PC onset under the age of 67 (odds ratio [OR] = 2.92; 95% confidence interval [CI], 1.10-7.86; P = 0.013). Multivariate logistic regression analysis confirmed this association (OR = 1.82; 95% CI, 1.03-3.22; P = 0.037). Furthermore, the homozygosity for the A-allele was associated with higher serum PSA levels (P = 0.027) and with the presence of circulating tumor cells in the blood of PC patients (P = 0.018).


CONCLUSIONS
Our results indicate that polymorphism in the PSA gene promoter may be an important biomarker for prostate cancer risk, especially for an earlier onset of PC.
Medeiros
Rui
R
Molecular Oncology Unit, Instituto Português de Oncologia, Porto, Portugal. mop06210@mail.telepac.pt
Morais
Antonio
A
Vasconcelos
André
A
Costa
Sandra
S
Pinto
Daniela
D
Oliveira
Jorge
J
Carvalho
Rodrigo
R
Lopes
Carlos
C
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012044:Regression Analysis; D012307:Risk Factors
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen