BMC medical genetics · 2014
Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Henríquez-Hernández Luis Alberto, Valenciano Almudena, Foro-Arnalot Palmira, Álvarez-Cubero María Jesús, Cozar 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-Melcón Juan Ignacio, Lara Pedro C
Аннотация
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.
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.
Предметные рубрики MeSH
Ataxia Telangiectasia Mutated ProteinsBiomarkersCohort StudiesDNA DamageDNA Ligase ATPDNA LigasesDNA RepairDNA-Binding ProteinsDisease ProgressionEndonucleasesGene FrequencyGenotypeHumansLogistic ModelsMaleNeoplasm GradingPolymorphism, Single NucleotidePrognosisProstate-Specific AntigenProstatic NeoplasmsRisk FactorsSpainTumor Suppressor Protein p53White PeopleX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D Protein