Abstract
21033 Background: Single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in androgen metabolism were suggested to influence the individual prostate cancer susceptibility and clinical course of the disease. To examine this correlation in Polish population, we have developed a case-control study to analyze whether SNPs in CYP17 (+34T/C), SRD5A2 (V89L and A49T) and UGT2B15 (D85Y) genes may influence prostate cancer risk. These SNPs were also examined for their correlation with clinical features of prostate cancer at diagnosis and disease progression to hormone-refractory state. Methods: The genomic DNA was extracted from blood samples from 182 men with histologically confirmed prostate cancer and 217 healthy men, randomly chosen from population. SNPs analyses were performed with standard molecular methods. Results: The case-control study has revealed that 85YY and 85DY variants in UGT2B15 were more prevalent among patients (83%) than in the control group (73.3%; p=0.02; OR=1.78). The +34CC genotype in CYP17 was more frequent in patients with distant metastasis (30.4%) than in patients with organ confined (T1/T2) or locally advanced (T3/T4) disease (10.2% and 22.6%, respectively; p<0.05). This variant also correlated with higher PSA level at diagnosis. The 89LL variant in SRD5A2 was more common in patients with poorly differentiated prostate cancer (Gleason >6; 17.8%) than in men with well differentiated tumor (5.4%; p=0.033, OR=3.78). The 85YY variant in UGT2B15 was more prevalent in patients that developed hormone-refractory prostate cancer within two years from the beginning of androgen blockade (47.2% vs 23.3%, p=0.025, OR=2.95). Also the analysis of progression-free survival time on hormonal therapy for D85Y polymorphism yield significant results (p=0.041, Gehan's generalized Wilcoxon test). Conclusions: The D85Y polymorphism in UGT2B15 seems to influence prostate cancer risk in Polish population. The analyzed SNPs also correlated with clinical stage and PSA level at diagnosis (+34T/C in CYP17), tumor histological grade (V89L in SRD5A2) and response to hormonal therapy (D85Y in UGT2B15). No significant financial relationships to disclose.
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