背景:前列腺癌(PCa)是一种雄激素依赖性疾病。尽管如此,单核苷酸多态性(SNPs)在编码雄激素代谢的基因中的作用仍未被研究.
目的:研究种系变异在细胞色素P45017A1(CYP17A1)和类固醇5α还原酶中的作用,PCa中的α-多肽1和2(SRD5A1和SRD5A2)基因。
方法:总共,这项多中心研究包括494例被诊断为非转移性局部PCa的连续西班牙患者,并使用BiotroveOpenArrayNTCycler对SRD5A1,SRD5A2和CYP17A1基因中的32个SNP进行了基因分型。临床数据可用。基因型和等位基因频率,以及单倍型分析,是使用基于网络的环境SNPator确定的。使用PASW统计15进行比较临床数据和SNP的所有其他统计分析。
结果:获得的呼叫率(确定为成功确定的百分比)为检测的97.3%。SRD5A1-rs3822430和rs1691053中共有2个SNP与诊断时的前列腺特异性抗原水平相关。此外,与AA-AA携带者相比,两种SNP的G携带者呈现初始前列腺特异性抗原水平>20ng/ml(Exp(B)=2.812,95%CI:1.397-5.657,P=0.004)的风险更高。单倍型分析显示,单倍型GCTTTGTAGTA的PCa非纯合患者出现更大的临床肿瘤大小的风险升高(Exp(B)=3.823,95%CI:1.280-11.416,P=0.016),Gleason评分较高(Exp(B)=2.808,95%CI:1.134-6.953,P=0.026)。
结论:SRD5A1中的SNP似乎影响西班牙PCa患者的临床特征。
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.
OBJECTIVE: 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.
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.