Title Page Genetic Variations of Genes Involved in Testosterone Metabolism are Associated to Prostate Cancer Progression: a Spanish Multicenter Study Authors:
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چکیده
Background. Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms in genes encoding androgen metabolism remains an unexplored area. Purpose. To investigate the role of germ-line variations in cytochrome P450 17A1 (CYP17A1), steroid-5-reductase, -polypeptide 1 and 2 (SRD5A1, SRD5A2) genes in PCa. Patients and Methods. 494 consecutive Spanish patients diagnosed with non-metastatic localized PCa were included in this multicenter study and were genotyped for 32 single nucleotide polymorphisms (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. Two SNPs in SRD5A1 – rs3822430 and rs1691053 – were associated to PSA level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of present initial PSA levels > 20 ng/mL (Exp(B) = 2.812, confidence interval (CI) 95% (1.397 – 5.657), p = 0.004) than those AA – AA carriers. Haplotype analyses showed that PCa patients nonhomozygous for the haplotype GCTTGTAGTA were at higher risk of present bigger clinical tumor size (Exp(B) = 3.823, CI95% (1.280 – 11.416), p = 0.016), and bigger Gleason score (Exp(B) = 2.808, CI95% (1.134 – 6.953), p = 0.026). Conclusions. Single nucleotide polymorphisms in SRD5A1 seem to condition the clinical characteristics of Spanish PCa patients.
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تاریخ انتشار 2015