Cornu Jean-Nicolas, Audet-Walsh Etienne, Drouin Sarah, Bigot Pierre, Valeri Antoine, Fournier Georges, Azzouzi Abdel-Rahmène, Roupret Morgan, Cormier Luc, Chanock Stephen, Guillemette Chantal, Cussenot Olivier, Lévesque Eric, Cancel-Tassin Géraldine
Academic Department of Urology, Hopital Tenon, AP-HP, UPMC University Paris 06, Paris, 75020, France.
GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France.
World J Urol. 2017 Feb;35(2):293-298. doi: 10.1007/s00345-016-1869-4. Epub 2016 Jun 8.
A few preliminary studies have suggested a link between some genetics variants and benign prostatic hyperplasia (BPH). Our goal was to study the link between a set of single nucleotide polymorphisms (SNPs) implicated in the steroid pathway and accurate measurement of prostate volume in a cohort of men who underwent radical prostatectomy.
Clinical and pathological data including prostate weight were obtained from 611 Caucasian patients with small volume, localized prostate cancer treated by radical prostatectomy. Patients were genotyped for 90 SNPs located inside or nearby genes implicated in the steroid pathway (Sequenom iPLEX). Correlation between prostate weight and genotypes from each SNP was studied by analysis of covariance, adjusted on age and tumor stage. A Bonferroni correction was applied, and the SNPs implicated were then incorporated in a multivariable model.
Seven SNPs located in or nearby genes implicated in steroid hormone metabolism were significantly associated with prostate volume: HSD17B2 (rs1119933), ESR2 (rs8006145), SULT2B1 (rs279451), NQO1 (rs2917670), ESR1 (rs1569788), GSTP1 (rs1138272), and CYP19A1 (rs17523880). Significant association was maintained after multivariate analysis for four SNPs, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. The strongest associations were found with variants in ESR1, ESR2, HSD17B2, and CYP19A1 genes, indicating a potential role of the estrogen signaling pathway in genesis of BPH.
Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.
一些初步研究表明某些基因变异与良性前列腺增生（BPH）之间存在联系。我们的目标是在一组接受根治性前列腺切除术的男性队列中，研究一组与类固醇途径相关的单核苷酸多态性（SNP）与前列腺体积精确测量之间的联系。
从611例接受根治性前列腺切除术治疗的小体积局限性前列腺癌白种患者中获取包括前列腺重量在内的临床和病理数据。对位于类固醇途径相关基因内部或附近的90个SNP进行基因分型（Sequenom iPLEX）。通过协方差分析研究前列腺重量与每个SNP基因型之间的相关性，并根据年龄和肿瘤分期进行调整。应用Bonferroni校正，然后将相关的SNP纳入多变量模型。
位于类固醇激素代谢相关基因内部或附近的7个SNP与前列腺体积显著相关：HSD17B2（rs1119933）、ESR2（rs8006145）、SULT2B1（rs279451）、NQO1（rs2917670）、ESR1（rs1569788）（rs1138272）和CYP19A1（rs17523880）。四个SNP在多变量分析后仍保持显著相关性，表明它们与前列腺体积独立相关。每个SNP与前列腺体积关联的效力与年龄的影响相当。在ESR1、ESR2、HSD17B2和CYP19A1基因变异中发现了最强的关联，表明雌激素信号通路在BPH发生中可能起作用。
我们的结果支持雌激素生物转化和信号通路参与BPH病理生理学过程。
