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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/35776

Title: Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression
Authors: Henríquez-Hernández, Luis Alberto
Valenciano, Almudena
Foro-Arnalot, Palmira
Álvarez-Cubero, María Jesús
Cózar Olmo, José Manuel
Suárez-Novo, José Francisco
Castells-Esteve, Manel
Fernández-Gonzalo, Pablo
De-Paula-Carranza, Belén
Ferrer, Montse
Guedea, Ferrán
Sancho-Pardo, Gemma
Craven-Bartle, Jordi
Ortiz-Gordillo, María José
Cabrera-Roldán, Patricia
Herrera-Ramos, Estefanía
Rodríguez-Gallego, Carlos
Rodríguez-Melcon, Juan Ignacio
Lara, Pedro C.
Issue Date: 2014
Abstract: 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.
Sponsorship: This work was subsidized by a grant from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad from Spain), ID: PI12/01867. Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC).
Publisher: Biomed Central
Keywords: Single nucleotide polymorphism
Prostate cancer
DNA repair
Spanish cohort
URI: http://hdl.handle.net/10481/35776
ISSN: 1471-2350
Citation: Henríquez-Hernández, L.A.; et al. Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression. BMC Medical Genetics, 15: 143 (2014). [http://hdl.handle.net/10481/35776]
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