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

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.

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 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 2016-04-28T11:11:01Z
dc.date.available 2016-09-30T02:00:05Z
dc.date.issued 2016
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.ca
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/pdfca
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.2015.63ca
dc.identifier.doi http://dx.doi.org/10.1038/pcan.2015.63
dc.identifier.issn 1365-7852
dc.identifier.uri http://hdl.handle.net/10230/26209
dc.language.iso engca
dc.publisher Nature publishing groupca
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.2015.63ca
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other ADNca
dc.subject.other Pròstata -- Càncer -- Espanyaca
dc.title Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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