参与睾酮代谢的基因中的遗传变异与前列腺癌进展相关：一项西班牙多中心研究。

Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.

作者信息

Henríquez-Hernández Luis Alberto, Valenciano Almudena, Foro-Arnalot Palmira, Álvarez-Cubero María Jesús, Cozar José Manuel, Suárez-Novo José Francisco, Castells-Esteve Manel, Fernández-Gonzalo Pablo, De-Paula-Carranza Belén, Ferrer Montse, Guedea Ferrán, Sancho-Pardo Gemma, Craven-Bartle Jordi, Ortiz-Gordillo María José, Cabrera-Roldán Patricia, Rodríguez-Melcón Juan Ignacio, Herrera-Ramos Estefanía, Rodríguez-Gallego Carlos, Lara Pedro C

机构信息

Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas, Spain; Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.

Instituto Canario de Investigación del Cáncer, Las Palmas, Spain.

出版信息

Urol Oncol. 2015 Jul;33(7):331.e1-7. doi: 10.1016/j.urolonc.2015.04.003. Epub 2015 May 7.

DOI:10.1016/j.urolonc.2015.04.003

PMID:25960412

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.

摘要

背景

前列腺癌（PCa）是一种雄激素依赖性疾病。然而，编码雄激素代谢的基因中的单核苷酸多态性（SNP）的作用仍是一个未被探索的领域。

目的

研究细胞色素P450 17A1（CYP17A1）和类固醇5α-还原酶α-多肽1和2（SRD5A1和SRD5A2）基因种系变异在前列腺癌中的作用。

患者与方法

本多中心研究共纳入494例连续诊断为非转移性局限性前列腺癌的西班牙患者，使用Biotrove OpenArray NT Cycler对SRD5A1、SRD5A2和CYP17A1基因中的32个SNP进行基因分型。可获得临床数据。使用基于网络的SNPator环境确定基因型和等位基因频率以及单倍型分析。使用PASW Statistics 15进行所有比较临床数据和SNP的其他统计分析。

结果

获得的检出率（确定为成功检测的百分比）为97.3%。SRD5A1中的两个SNP——rs3822430和rs1691053——与诊断时的前列腺特异性抗原水平相关。此外，这两个SNP的G等位基因携带者出现初始前列腺特异性抗原水平>20ng/ml的风险高于AA-AA基因型携带者（Exp(B)=2.812，95%CI：1.397-5.657，P=0.004）。单倍型分析显示，非纯合子GCTTGTAGTA单倍型的前列腺癌患者出现更大临床肿瘤大小的风险升高（Exp(B)=3.823，95%CI：1.280-11.416，P=0.016），且Gleason评分更高（Exp(B)=2.808，95%CI：1.134-6.953，P=0.026）。