Correlation between prostate volume and single nucleotide polymorphisms implicated in the steroid pathway.
OBJECTIVE
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.


CONCLUSIONS
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.
Academic Department of Urology, Hopital Tenon, AP-HP, UPMC University Paris 06, Paris, 75020, France. jeannicolas.cornu@gmail.com.|GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France. jeannicolas.cornu@gmail.com.
Jean-Nicolas
JN
Cornu
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Québec, Canada.
Etienne
E
Audet-Walsh
GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France.|Academic Department of Urology, Hopital Pitié-Salpétrière, AP-HP, UPMC University Paris 06, Paris, 75013, France.
Sarah
S
Drouin
Academic Department of Urology, CHU Angers, Angers, 49000, France.
Pierre
P
Bigot
Academic Department of Urology, CHU Brest, Brest, 29000, France.|CeRePP, Paris, 75020, France.
Antoine
A
Valeri
Academic Department of Urology, CHU Brest, Brest, 29000, France.|CeRePP, Paris, 75020, France.
Georges
G
Fournier
Academic Department of Urology, CHU Angers, Angers, 49000, France.|CeRePP, Paris, 75020, France.
Abdel-Rahmène
AR
Azzouzi
GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France.|Academic Department of Urology, Hopital Pitié-Salpétrière, AP-HP, UPMC University Paris 06, Paris, 75013, France.|CeRePP, Paris, 75020, France.
Morgan
M
Roupret
CeRePP, Paris, 75020, France.|Academic Department of Urology, CHU Dijon, Dijon, 21000, France.
Luc
L
Cormier
Laboratory of Translational Genomics, Department of Cancer Epidemiology and Genetics, NCI/NIH Bethesda, Bethesda, MD, USA.
Stephen
S
Chanock
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Québec, Canada.
Chantal
C
Guillemette
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.|CeRePP, Paris, 75020, France.
Olivier
O
Cussenot
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Québec, Canada.
Eric
E
Lévesque
GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France.|CeRePP, Paris, 75020, France.
Géraldine
G
Cancel-Tassin
D000328:Adult; D000368:Aged; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D015398:Signal Transduction / Q000235:genetics*
D012739:Gonadal Steroid Hormones
Prostate weight; Prostatectomy; Single nucleotide polymorphisms; Steroid pathway