Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression
Por:
Henriquez-Hernandez, LA, Valenciano, A, Foro-Arnalot, P, Alvarez-Cubero, MJ, Cozar, JM, Suarez-Novo, JF, Castells-Esteve, M, Fernandez-Gonzalo, P, De-Paula-Carranza, B, Ferrer, M, Guedea, F, Sancho-Pardo, G, Craven-Bartle, J, Ortiz-Gordillo, MJ, Cabrera-Roldan, P, Herrera-Ramos, E, Rodriguez-Gallego, C, Rodriguez-Melcon, JI, Lara, PC
Publicada:
24 dic 2014
Resumen:
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 (R) 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.
Filiaciones:
Henriquez-Hernandez, LA:
Hosp Univ Gran Canaria Dr Negrin, Dept Radiat Oncol, Las Palmas Gran Canaria 35010, Spain
Inst Canario Invest Cancer, Las Palmas Gran Canaria, Spain
Univ Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain
Valenciano, A:
Inst Canario Invest Cancer, Las Palmas Gran Canaria, Spain
Foro-Arnalot, P:
Univ Pompeu Fabra, Hosp Esperanza, Inst Oncol Radioterap, Barcelona, Spain
Alvarez-Cubero, MJ:
Univ Granada, Fac Med, Legal Med & Toxicol Dept, Lab Genet Identificat, Granada, Spain
Pfizer Univ Granada Andalusian, Govt Ctr Genom & Oncol Res, GENYO, Granada, Spain
Cozar, JM:
Hosp Univ Virgen Nieves, Dept Urol, Granada, Spain
Suarez-Novo, JF:
Hosp Univ Bellvitge, Hosp Llobregat, Dept Urol, Lhospitalet De Llobregat, Spain
Castells-Esteve, M:
Hosp Univ Bellvitge, Hosp Llobregat, Dept Urol, Lhospitalet De Llobregat, Spain
Fernandez-Gonzalo, P:
Dept Radiat Oncol, Onkologikoa, Guipuzcoa, Spain
De-Paula-Carranza, B:
Dept Radiat Oncol, Onkologikoa, Guipuzcoa, Spain
Ferrer, M:
Inst Recerca Hosp Mar IMIM, Hlth Serv Res Grp, Barcelona, Spain
Guedea, F:
ICO, Hosp Llobregat, Dept Radiat Oncol, Puerto Del Carmen, Spain
Sancho-Pardo, G:
Hosp Santa Creu & Sant Pau, Dept Radiat Oncol, Barcelona, Spain
Craven-Bartle, J:
Hosp Santa Creu & Sant Pau, Dept Radiat Oncol, Barcelona, Spain
Ortiz-Gordillo, MJ:
Hosp Univ Virgen Rocio, Dept Radiat Oncol, Seville, Spain
Cabrera-Roldan, P:
Hosp Univ Virgen Rocio, Dept Radiat Oncol, Seville, Spain
Herrera-Ramos, E:
Hosp Univ Gran Canaria Dr Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain
Univ Palmas Gran Canaria, Dept Med & Surg Sci, Las Palmas Gran Canaria, Spain
Rodriguez-Gallego, C:
Hosp Univ Gran Canaria Dr Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain
Univ Palmas Gran Canaria, Dept Med & Surg Sci, Las Palmas Gran Canaria, Spain
Rodriguez-Melcon, JI:
Hosp Univ Gran Canaria Dr Negrin, Dept Radiat Oncol, Las Palmas Gran Canaria 35010, Spain
Inst Canario Invest Cancer, Las Palmas Gran Canaria, Spain
Univ Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain
Lara, PC:
Hosp Univ Gran Canaria Dr Negrin, Dept Radiat Oncol, Las Palmas Gran Canaria 35010, Spain
Inst Canario Invest Cancer, Las Palmas Gran Canaria, Spain
Univ Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain
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