BACKGROUND: The relationship between polymorphisms in the hydroxysteroid (17-beta) dehydrogenase (HSD17B) family of genes, which are involved in steroid hormone biotransformation, and the risk of prostate cancer (PCa) progression remains unexplored. OBJECTIVE: Determine whether inherited variations in HSD17B genes are associated with PCa progression. DESIGN, SETTING, AND PARTICIPANTS: We studied two independent Caucasian cohorts composed of 526 men with organ-confined PCa and 213 men with advanced disease who had a median follow-up of 7.4 yr and 7.8 yr after surgery, respectively. MEASUREMENTS: Patients with localised PCa were genotyped for 88 haplotype-tagging single nucleotide polymorphisms in HSD17B type 1 (HSD17B1), type 2 (HSD17B2), type 3 (HSD17B3), type 4 (HSD17B4), type 5 (HSD17B5), and type 12 (HSD17B12), and their prognostic significance on disease progression was assessed using Kaplan-Meier survival curves and Cox regression models. Positive findings were then investigated in advanced disease. RESULTS AND LIMITATIONS: After adjusting for known risk factors, 12 SNPs distributed across HSD17B2, HSD17B3, and HSD17B12 were significantly associated with risk of biochemical recurrence (BCR) in localised PCa (for variants in HSD17B2: hazard ratio [HR]: 1.92-2.93; p=0.025-0.004). In addition, four variants of HSD17B2 (rs1364287, rs2955162, rs1119933, rs9934209) were significantly associated with progression-free survival (HR: 2.96-4.69; p=0.004-0.00005) and overall survival in advanced disease (HR: 3.98-8.14; p=0.003-0.00002). Four variants of HSD17B3 and HSD17B12 were associated with a reduced risk of BCR (HR: 0.51-0.65; p=0.020-0.036) but not with progression in advanced disease. These results were generated mainly in Caucasians and should be studied in other ethnic groups. CONCLUSIONS: This study suggests a prominent role for common genetic variants in the HSD17B2 pathway in PCa progression.
BACKGROUND: The relationship between polymorphisms in the hydroxysteroid (17-beta) dehydrogenase (HSD17B) family of genes, which are involved in steroid hormone biotransformation, and the risk of prostate cancer (PCa) progression remains unexplored. OBJECTIVE: Determine whether inherited variations in HSD17B genes are associated with PCa progression. DESIGN, SETTING, AND PARTICIPANTS: We studied two independent Caucasian cohorts composed of 526 men with organ-confined PCa and 213 men with advanced disease who had a median follow-up of 7.4 yr and 7.8 yr after surgery, respectively. MEASUREMENTS: Patients with localised PCa were genotyped for 88 haplotype-tagging single nucleotide polymorphisms in HSD17B type 1 (HSD17B1), type 2 (HSD17B2), type 3 (HSD17B3), type 4 (HSD17B4), type 5 (HSD17B5), and type 12 (HSD17B12), and their prognostic significance on disease progression was assessed using Kaplan-Meier survival curves and Cox regression models. Positive findings were then investigated in advanced disease. RESULTS AND LIMITATIONS: After adjusting for known risk factors, 12 SNPs distributed across HSD17B2, HSD17B3, and HSD17B12 were significantly associated with risk of biochemical recurrence (BCR) in localised PCa (for variants in HSD17B2: hazard ratio [HR]: 1.92-2.93; p=0.025-0.004). In addition, four variants of HSD17B2 (rs1364287, rs2955162, rs1119933, rs9934209) were significantly associated with progression-free survival (HR: 2.96-4.69; p=0.004-0.00005) and overall survival in advanced disease (HR: 3.98-8.14; p=0.003-0.00002). Four variants of HSD17B3 and HSD17B12 were associated with a reduced risk of BCR (HR: 0.51-0.65; p=0.020-0.036) but not with progression in advanced disease. These results were generated mainly in Caucasians and should be studied in other ethnic groups. CONCLUSIONS: This study suggests a prominent role for common genetic variants in the HSD17B2 pathway in PCa progression.
Authors: Jean-Nicolas Cornu; Etienne Audet-Walsh; Sarah Drouin; Pierre Bigot; Antoine Valeri; Georges Fournier; Abdel-Rahmène Azzouzi; Morgan Roupret; Luc Cormier; Stephen Chanock; Chantal Guillemette; Olivier Cussenot; Eric Lévesque; Géraldine Cancel-Tassin Journal: World J Urol Date: 2016-06-08 Impact factor: 4.226
Authors: Gonda Konings; Linda Brentjens; Bert Delvoux; Tero Linnanen; Karlijn Cornel; Pasi Koskimies; Marlies Bongers; Roy Kruitwagen; Sofia Xanthoulea; Andrea Romano Journal: Front Pharmacol Date: 2018-09-19 Impact factor: 5.810
Authors: Thomas Van den Broeck; Steven Joniau; Liesbeth Clinckemalie; Christine Helsen; Stefan Prekovic; Lien Spans; Lorenzo Tosco; Hendrik Van Poppel; Frank Claessens Journal: Biomed Res Int Date: 2014-02-19 Impact factor: 3.411
Authors: Inmaculada Robles-Fernandez; Luis Javier Martinez-Gonzalez; Manrique Pascual-Geler; Jose Manuel Cozar; Ignacio Puche-Sanz; Maria Jose Serrano; Jose Antonio Lorente; Maria Jesus Alvarez-Cubero Journal: PLoS One Date: 2017-10-05 Impact factor: 3.240