Jean-Nicolas Cornu1,2, Etienne Audet-Walsh3, Sarah Drouin4,5, Pierre Bigot6, Antoine Valeri7,8, Georges Fournier7,8, Abdel-Rahmène Azzouzi6,8, Morgan Roupret4,5,8, Luc Cormier8,9, Stephen Chanock10, Chantal Guillemette3, Olivier Cussenot11,4,8, Eric Lévesque3, Géraldine Cancel-Tassin4,8. 1. Academic Department of Urology, Hopital Tenon, AP-HP, UPMC University Paris 06, Paris, 75020, France. jeannicolas.cornu@gmail.com. 2. GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France. jeannicolas.cornu@gmail.com. 3. Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Québec, Canada. 4. GRC No 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC University Paris 06, Paris, 75020, France. 5. Academic Department of Urology, Hopital Pitié-Salpétrière, AP-HP, UPMC University Paris 06, Paris, 75013, France. 6. Academic Department of Urology, CHU Angers, Angers, 49000, France. 7. Academic Department of Urology, CHU Brest, Brest, 29000, France. 8. CeRePP, Paris, 75020, France. 9. Academic Department of Urology, CHU Dijon, Dijon, 21000, France. 10. Laboratory of Translational Genomics, Department of Cancer Epidemiology and Genetics, NCI/NIH Bethesda, Bethesda, MD, USA. 11. Academic Department of Urology, Hopital Tenon, AP-HP, UPMC University Paris 06, Paris, 75020, France.
Abstract
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.
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.
Entities:
Keywords:
Prostate weight; Prostatectomy; Single nucleotide polymorphisms; Steroid pathway
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