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Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

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dc.contributor.author Henríquez Hernández, Luis Alberto
dc.contributor.author Valenciano, Almudena
dc.contributor.author Foro Arnalot, Palmira
dc.contributor.author Álvarez Cubero, María Jesús
dc.contributor.author Cozar, José Manuel
dc.contributor.author Suárez Novo, José Francisco
dc.contributor.author Castells Esteve, Manel
dc.contributor.author Fernández Gonzalo, Pablo
dc.contributor.author De-Paula Carranza, Belén
dc.contributor.author Ferrer Forés, Maria Montserrat
dc.contributor.author Guedea, Ferrán
dc.contributor.author Sancho-Pardo, Gemma
dc.contributor.author Craven-Bartle, Jordi
dc.contributor.author Ortiz Gordillo, María José
dc.contributor.author Cabrera Roldán, Patricia
dc.contributor.author Rodríguez Melcón, Juan Ignacio
dc.contributor.author Herrera Ramos, Estefanía
dc.contributor.author Rodríguez Gallego, Carlos
dc.contributor.author Lara, Pedro C.
dc.date.accessioned 2016-04-28T11:11:01Z
dc.date.available 2016-09-30T02:00:05Z
dc.date.issued 2016
dc.identifier.citation Henríquez-Hernández LA, Valenciano A, Foro-Arnalot P, Álvarez-Cubero MJ, Cozar JM, Suárez-Novo JF. et al. Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population. Prostate Cancer Prostatic Dis. 2016 Mar;19(1):28-34. doi: 10.1038/pcan.2015.63
dc.identifier.issn 1365-7852
dc.identifier.uri http://hdl.handle.net/10230/26209
dc.description.abstract BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.
dc.description.sponsorship This work was subsidized by grants from the Instituto de Salud Carlos III (Ministerio de. Economía y Competitividad from Spain), ID: PI12/01867 and PI13/00412; and Instituto Canario de Investigación del Cáncer (ICIC-GR-F-14/11). Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature publishing group
dc.relation.ispartof Prostate Cancer and Prostatic Diseases. 2016 Mar;19(1):28-34
dc.rights c) Nature Publishing Group http://dx.doi.org/10.1038/pcan.2015.63
dc.subject.other ADN
dc.subject.other Pròstata -- Càncer -- Espanya
dc.title Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/pcan.2015.63
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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