BACKGROUND: Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles. RESULTS: The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.
BACKGROUND:Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles. RESULTS: The SRD5A2V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2V89L polymorphism may modify the risk conferred by this polymorphism.
Authors: J F Dorgan; D Albanes; J Virtamo; O P Heinonen; D W Chandler; M Galmarini; L M McShane; M J Barrett; J Tangrea; P R Taylor Journal: Cancer Epidemiol Biomarkers Prev Date: 1998-12 Impact factor: 4.254
Authors: N Makridakis; R K Ross; M C Pike; L Chang; F Z Stanczyk; L N Kolonel; C Y Shi; M C Yu; B E Henderson; J K Reichardt Journal: Cancer Res Date: 1997-03-15 Impact factor: 12.701
Authors: Luis Alberto Henríquez-Hernández; Almudena Valenciano; Palmira Foro-Arnalot; María Jesús Álvarez-Cubero; José Manuel Cozar; José Francisco Suárez-Novo; Manel Castells-Esteve; Pablo Fernández-Gonzalo; Belén De-Paula-Carranza; Montse Ferrer; Ferrán Guedea; Gemma Sancho-Pardo; Jordi Craven-Bartle; María José Ortiz-Gordillo; Patricia Cabrera-Roldán; Estefanía Herrera-Ramos; Carlos Rodríguez-Gallego; Pedro C Lara Journal: J Genet Date: 2015-06 Impact factor: 1.166
Authors: Tristan M Sissung; Douglas K Price; Marzia Del Re; Ariel M Ley; Elisa Giovannetti; William D Figg; Romano Danesi Journal: Biochim Biophys Acta Date: 2014-09-06
Authors: Pedro Fernandez; Charnita M Zeigler-Johnson; Elaine Spangler; André van der Merwe; Mohamed Jalloh; Serigne M Gueye; Timothy R Rebbeck Journal: Prostate Cancer Date: 2012-10-02
Authors: Angeline S Andrew; Ting Hu; Jian Gu; Jiang Gui; Yuanqing Ye; Carmen J Marsit; Karl T Kelsey; Alan R Schned; Sam A Tanyos; Eben M Pendleton; Rebecca A Mason; Elaine V Morlock; Michael S Zens; Zhongze Li; Jason H Moore; Xifeng Wu; Margaret R Karagas Journal: PLoS One Date: 2012-12-19 Impact factor: 3.240