title: Linkage between polymorphisms in the prostate specific antigen ARE1 gene region, prostate cancer risk, and circulating tumor cells.
abstract: 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.
authors.affiliation: Molecular Oncology Unit, Instituto Português de Oncologia, Porto, Portugal. mop06210@mail.telepac.pt
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: Antonio
authors.initials: A
authors.lastname: Morais
authors.forename: André
authors.initials: A
authors.lastname: Vasconcelos
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Daniela
authors.initials: D
authors.lastname: Pinto
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carvalho
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen