Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.

Henríquez Hernández, Luis Alberto; Valenciano, Almudena; Foro Arnalot, Palmira; Álvarez Cubero, María Jesús; Cozar, José Manuel; Suárez Novo, José Francisco; Castells Esteve, Manel; Fernández Gonzalo, Pablo; De-Paula Carranza, Belén; Ferrer Forés, Maria Montserrat; Guedea, Ferrán; Sancho-Pardo, Gemma; Craven-Bartle, Jordi; Ortiz Gordillo, María José; Cabrera Roldán, Patricia; Rodríguez Melcón, Juan Ignacio; Herrera Ramos, Estefanía; Rodríguez Gallego, Carlos; Lara, Pedro C.

Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.

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dc.contributor.author Henríquez Hernández, Luis Albertoca
dc.contributor.author Valenciano, Almudenaca
dc.contributor.author Foro Arnalot, Palmiraca
dc.contributor.author Álvarez Cubero, María Jesúsca
dc.contributor.author Cozar, José Manuelca
dc.contributor.author Suárez Novo, José Franciscoca
dc.contributor.author Castells Esteve, Manelca
dc.contributor.author Fernández Gonzalo, Pabloca
dc.contributor.author De-Paula Carranza, Belénca
dc.contributor.author Ferrer Forés, Maria Montserratca
dc.contributor.author Guedea, Ferránca
dc.contributor.author Sancho-Pardo, Gemmaca
dc.contributor.author Craven-Bartle, Jordica
dc.contributor.author Ortiz Gordillo, María Joséca
dc.contributor.author Cabrera Roldán, Patriciaca
dc.contributor.author Rodríguez Melcón, Juan Ignacioca
dc.contributor.author Herrera Ramos, Estefaníaca
dc.contributor.author Rodríguez Gallego, Carlosca
dc.contributor.author Lara, Pedro C.ca
dc.date.accessioned 2015-07-01T11:15:56Z
dc.date.available 2016-07-31T02:00:04Z
dc.date.issued 2015
dc.description.abstract BACKGROUND: Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area. PURPOSE: To investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa. PATIENTS AND METHODS: In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15. RESULTS: The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026). CONCLUSIONS: SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa. Copyright © 2015 Elsevier Inc. All rights reserved.ca
dc.description.sponsorship This work was subsidized by Grants from the Instituto de Salud Carlos III, Madrid, Spain (Ministerio de Economía y Competitividad, Spain), ID: PI12/01867 and/nPI13/00412; and Instituto Canario de Investigación del Cáncer, Canary Islands, Spain (ID: ICIC-GR-F-14/11). Almudena Valenciano received a Grant from the/nInstituto Canario de Investigación del Cáncer (ICIC).
dc.format.mimetype application/pdfca
dc.identifier.citation Henríquez-Hernández LA, Valenciano A, Foro-Arnalot P, Álvarez-Cubero MJ, Cozar JM, Suárez-Novo JF. et al. Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study. Urol Oncol. 2015 Jul;33(7):331.e1-7. doi: 10.1016/j.urolonc.2015.04.003ca
dc.identifier.doi http://dx.doi.org/10.1016/j.urolonc.2015.04.003
dc.identifier.issn 1078-1439
dc.identifier.uri http://hdl.handle.net/10230/24574
dc.language.iso engca
dc.publisher Elsevierca
dc.relation.ispartof Urologic Oncology. 2015 Jul;33(7):331.e1-7
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Pròstata -- Càncerca
dc.title Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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