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The identification of men predisposed to advanced prostate cancer is important as it influences diagnostic and treatment modalities. In this study, we examined variants in the prostate specific antigen (PSA) gene and their possible association with the risk of prostate cancer, the occurrence of advanced disease, and serum PSA levels. Three functional single nucleotide polymorphisms (SNPs) in the enhancer region of the PSA gene, -5429T/G, -5412T/C and -4643A/G, were genotyped in 84 prostate cancer cases and 109 controls using the SNaPshotTM multiplex technique. Prostate cancer patients were divided into two groups: those with localized (n=37) and advanced (n=36) disease. Between these two groups, two SNPs, -5429T/G and -5412T/C, were found to have statistically significant differences in PSA genotype frequencies. The heterozygous genotype in the PSA gene conferred an increased risk of advanced prostate cancer. After age-adjustment, the estimated OR and 95% CI for -5429T/G and -5412T/C was 3.59 (1.16-11.09; P&lt;0.02), and 3.26 (1.04-10.22; P&lt;0.02), respectively, whereas for -4643A/G, the OR was 2.46 (0.86-7.04; P&lt;0.08). The haplotype -5429G/-5412C/-4643G with 11% frequency conferred a 3.5-fold increased risk of advanced prostate cancer (95% CI = 1.02-11.76; P&lt;0.051). Genotype distribution between the controls and prostate cancer cases did not demonstrate a statistically significant difference (P&gt;0.05). Genotype-based serum PSA levels for each SNP were also observed to be similar (P&gt;0.05). Heterozygosity observed in the PSA gene enhancer region contributes substantially to the occurrence of advanced prostate cancer. The identification of men at risk for advanced disease by PSA genotype may aid in determining the most effective therapeutic strategy, with the aim of improving the quality of life of patients.

Genetic variants in the distal enhancer region of the PSA gene and their implication in the occurrence of advanced prostate cancer