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