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Open Access 01-12-2014 | Research article

Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression

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

Published in: BMC Medical Genetics | Issue 1/2014

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.

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Title: Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression
Authors: Luis Alberto Henríquez-Hernández
Almudena Valenciano
Palmira Foro-Arnalot
María Jesús Álvarez-Cubero
José Manuel Cozar
José Francisco Suárez-Novo
Manel Castells-Esteve
Pablo Fernández-Gonzalo
Belén De-Paula-Carranza
Montse Ferrer
Ferrán Guedea
Gemma Sancho-Pardo
Jordi Craven-Bartle
María José Ortiz-Gordillo
Patricia Cabrera-Roldán
Estefanía Herrera-Ramos
Carlos Rodríguez-Gallego
Juan Ignacio Rodríguez-Melcón
Pedro C Lara
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2014
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-014-0143-0

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Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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