title: Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression.
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.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Henríquez-Hernández
authors.forename: Almudena
authors.initials: A
authors.lastname: Valenciano
authors.forename: Palmira
authors.initials: P
authors.lastname: Foro-Arnalot
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Álvarez-Cubero
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Cozar
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Suárez-Novo
authors.forename: Manel
authors.initials: M
authors.lastname: Castells-Esteve
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernández-Gonzalo
authors.forename: Belén
authors.initials: B
authors.lastname: De-Paula-Carranza
authors.forename: Montse
authors.initials: M
authors.lastname: Ferrer
authors.forename: Ferrán
authors.initials: F
authors.lastname: Guedea
authors.forename: Gemma
authors.initials: G
authors.lastname: Sancho-Pardo
authors.forename: Jordi
authors.initials: J
authors.lastname: Craven-Bartle
authors.forename: María José
authors.initials: MJ
authors.lastname: Ortiz-Gordillo
authors.forename: Patricia
authors.initials: P
authors.lastname: Cabrera-Roldán
authors.forename: Estefanía
authors.initials: E
authors.lastname: Herrera-Ramos
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodríguez-Gallego
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Rodríguez-Melcón
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Lara
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004249:DNA Damage / Q000235:genetics; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D004720:Endonucleases / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044465:White People / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D017430:Prostate-Specific Antigen; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP