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Basic Research

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

Prostate Cancer and Prostatic Diseases volume 19, pages 28–34 (2016)Cite this article

Subjects

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.

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Acknowledgements

We thank the technical support from the Immunology Department (Hospital Universitario de Gran Canaria Dr Negrín) staff: Nereida González-Quevedo and Yanira Florido-Ortega. 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). The founders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas,, Spain

    L A Henríquez-Hernández, J I Rodríguez-Melcón & P C Lara

  2. Instituto Canario de Investigación del Cáncer,, Las Palmas,, Spain

    L A Henríquez-Hernández, A Valenciano, J I Rodríguez-Melcón & P C Lara

  3. Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Las Palmas,, Spain

    L A Henríquez-Hernández & P C Lara

  4. Radiation Oncology Department, Institud d'Oncologia Radioteràpica, Hospital de la Esperanza, Parc de Salut Mar, Barcelona,, Spain

    P Foro-Arnalot

  5. Legal Medicine and Toxicology Department, Laboratory of Genetic Identification, Facultad de Medicina, Universidad de Granada, Granada, Spain

    M J Álvarez-Cubero

  6. GENYO, Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research, Granada,, Spain

    M J Álvarez-Cubero

  7. Department of Urology, Hospital Universitario Virgen de las Nieves, Granada, Spain

    J M Cozar

  8. Department of Urology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona,, Spain

    J F Suárez-Novo & M Castells-Esteve

  9. Radiation Oncology Department, Onkologikoa, Guipuzcoa,, Spain

    P Fernández-Gonzalo & B De-Paula-Carranza

  10. Health Services Research Group, Institut de Recerca Hospital del Mar (IMIM), Barcelona, Spain

    M Ferrer

  11. Department of Radiation Oncology, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona,, Spain

    F Guedea

  12. Radiation Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona,, Spain

    G Sancho-Pardo & J Craven-Bartle

  13. Radiation Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla,, Spain

    M J Ortiz-Gordillo & P Cabrera-Roldán

  14. Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain

    E Herrera-Ramos & C Rodríguez-Gallego

  15. Department of Medical and Surgical Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas,, Spain

    E Herrera-Ramos

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  1. L A Henríquez-Hernández
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  2. A Valenciano
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Correspondence to L A Henríquez-Hernández.

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Henríquez-Hernández, L., Valenciano, A., Foro-Arnalot, P. 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 19, 28–34 (2016). https://doi.org/10.1038/pcan.2015.63

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