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

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. Prostate Cancer and Prostatic Diseases advance online publication, 12 January 2016; doi:10. 1038/pcan. 2015. 63.

Prostate cancer and prostatic diseases. 2016 Jan 12 [Epub ahead of print]

L A Henríquez-Hernández, A Valenciano, P Foro-Arnalot, M J Álvarez-Cubero, J M Cozar, J F Suárez-Novo, M Castells-Esteve, P Fernández-Gonzalo, B De-Paula-Carranza, M Ferrer, F Guedea, G Sancho-Pardo, J Craven-Bartle, M J Ortiz-Gordillo, P Cabrera-Roldán, J I Rodríguez-Melcón, E Herrera-Ramos, C Rodríguez-Gallego, P C Lara

Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. , Instituto Canario de Investigación del Cáncer, Las Palmas, Spain. , Radiation Oncology Department, Institud d'Oncologia Radioteràpica, Hospital de la Esperanza, Parc de Salut Mar, Barcelona, Spain. , Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Facultad de Medicina, Universidad de Granada, Granada, Spain. , Department of Urology, Hospital Universitario Virgen de las Nieves, Granada, Spain. , Department of Urology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. , Department of Urology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. , Radiation Oncology Department, Onkologikoa, Guipuzcoa, Spain. , Radiation Oncology Department, Onkologikoa, Guipuzcoa, Spain. , Health Services Research Group, Institut de Recerca Hospital del Mar (IMIM), Barcelona, Spain. , Department of Radiation Oncology, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona, Spain. , Radiation Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. , Radiation Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. , Radiation Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain. , Radiation Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain. , Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. , Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. , Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. , Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain.

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