Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression
Henríquez-Hernández, Luis Alberto (Universidad de Las Palmas de Gran Canaria)
Valenciano, Almudena (Instituto Canario de Investigación del Cáncer)
Foro, Palmira (Parc de Salut MAR de Barcelona)
Álvarez-Cubero, María Jesús (Universidad de Granada)
Cozar, José Manuel (Hospital Universitario Virgen de las Nieves (Granada))
Suárez-Novo, José Francisco (Hospital Universitari de Bellvitge)
Castells-Esteve, Manel (Hospital Universitari de Bellvitge)
Fernández-Gonzalo, Pablo (Radiation Oncology Department)
De-Paula-Carranza, Belén (Radiation Oncology Department)
Ferrer, Montse (Institut Hospital del Mar d'Investigacions Mèdiques)
Guedea, Ferrán (Institut Català d'Oncologia)
Sancho-Pardo, Gemma (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Craven-Bartle, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Ortiz-Gordillo, María José (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Cabrera-Roldán, Patricia (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Herrera-Ramos, Estefanía (Universidad de Las Palmas de Gran Canaria)
Rodríguez-Gallego, Carlos (Universidad de Las Palmas de Gran Canaria)
Rodríguez-Melcón, Juan Ignacio (Instituto Canario de Investigación del Cáncer)
Lara, PedroC. (Universidad de Las Palmas de Gran Canaria)
Universitat Autònoma de Barcelona

Fecha:	2014
Resumen:	Background: Besides serum levels of PSA, there is a lack of prostate cancer specific biomarkers. It is need to develop new biological markers associated with the tumor behavior which would be valuable to better individualize treatment. The aim of this study was to elucidate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and prostate cancer progression. Methods: A total of 494 prostate cancer patients from a Spanish multicenter study were genotyped for 10 SNPs in XRCC1, ERCC2, ERCC1, LIG4, ATM and TP53 genes. The SNP genotyping was made 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: SNPs rs11615 (ERCC1) and rs17503908 (ATM) appeared as risk factors for prostate cancer aggressiveness. Patients wild homozygous for these SNPs (AA and TT, respectively) were at higher risk for developing cT2b - cT4 (OR = 2. 21 (confidence interval (CI) 95% 1. 47 - 3. 31), p < 0. 001) and Gleason scores ≥ 7 (OR = 2. 22 (CI 95% 1. 38 - 3. 57), p < 0. 001), respectively. Moreover, those patients wild homozygous for both SNPs had the greatest risk of presenting D'Amico high-risk tumors (OR = 2. 57 (CI 95% 1. 28 - 5. 16)). Conclusions: Genetic variants at DNA repair genes are associated with prostate cancer progression, and would be taken into account when assessing the malignancy of prostate cancer.
Ayudas:	Ministerio de Economía y Competitividad PI12/01867
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	ATM ; DNA repair ; ERCC1 ; OpenArray ; Prostate cancer ; Single nucleotide polymorphism ; Spanish cohort
Publicado en:	BMC Medical Genetics, Vol. 15 Núm. 1 (december 2014) , p. 143, ISSN 1471-2350

DOI: 10.1186/s12881-014-0143-0
PMID: 25540025

7 p, 474.9 KB

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