TY - JOUR
T1 - Correlation between prostate volume and single nucleotide polymorphisms implicated in the steroid pathway
AU - Cornu, Jean Nicolas
AU - Audet-Walsh, Etienne
AU - Drouin, Sarah
AU - Bigot, Pierre
AU - Valeri, Antoine
AU - Fournier, Georges
AU - Azzouzi, Abdel Rahmène
AU - Roupret, Morgan
AU - Cormier, Luc
AU - Chanock, Stephen
AU - Guillemette, Chantal
AU - Cussenot, Olivier
AU - Lévesque, Eric
AU - Cancel-Tassin, Géraldine
N1 - Funding Information:
We would like to thank Cécile Gaffory and Valérie Ondet for technical assistance. This work was supported by grant from the Institut National de Cancer (PHRC AOM06209), Cancer Research Society to C.G., and Prostate Cancer Canada to E.L. (DS2013-22). E.L. is a recipient of a Prostate Cancer Canada rising star award (RS2013-55) and a CIHR clinician-scientist phase 2 award. E.A.W. was a recipient of a postdoctoral fellowship award from the Canadian Institutes of Health Research. C.G. holds the Canada Research Chair in Pharmacogenomics.
Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Objectives: 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. Methods: 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. Results and limitations: 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. Conclusions: Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.
AB - Objectives: 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. Methods: 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. Results and limitations: 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. Conclusions: Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.
KW - Prostate weight
KW - Prostatectomy
KW - Single nucleotide polymorphisms
KW - Steroid pathway
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U2 - 10.1007/s00345-016-1869-4
DO - 10.1007/s00345-016-1869-4
M3 - Article
C2 - 27277477
AN - SCOPUS:84976319625
SN - 0724-4983
VL - 35
SP - 293
EP - 298
JO - World journal of urology
JF - World journal of urology
IS - 2
ER -