AI Article Synopsis
- - The study investigates the impact of genetic variations in specific androgen metabolism genes (CYP17A1, SRD5A1, and SRD5A2) on prostate cancer risk and characteristics among Spanish patients.
- - Researchers analyzed 494 patients with nonmetastatic localized prostate cancer, focusing on 32 single nucleotide polymorphisms (SNPs) and found significant associations between certain SNPs in the SRD5A1 gene and higher prostate-specific antigen levels at diagnosis.
- - Results indicated that nonhomozygous patients for a specific haplotype demonstrated a significantly greater risk of larger tumor size and higher Gleason scores, suggesting that SNPs in SRD5A1 may influence the severity of
Article Abstract
Background: Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area.
Purpose: To investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa.
Patients And Methods: In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15.
Results: The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026).
Conclusions: SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa.
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| http://dx.doi.org/10.1016/j.urolonc.2015.04.003 | DOI Listing |
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