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

被引：13

作者：

Henriquez-Hernandez, L. A. ^{[1
,2
,3
]}

Valenciano, A. ^{[2
]}

Foro-Arnalot, P. ^{[4
]}

Alvarez-Cubero, M. J. ^{[5
,6
]}

Cozar, J. M. ^{[7
]}

Suarez-Novo, J. F. ^{[8
]}

Castells-Esteve, M. ^{[8
]}

Fernandez-Gonzalo, P. ^{[9
]}

De-Paula-Carranza, B. ^{[9
]}

Ferrer, M. ^{[10
]}

Guedea, F. ^{[11
]}

Sancho-Pardo, G. ^{[12
]}

Craven-Bartle, J. ^{[12
]}

Ortiz-Gordillo, M. J. ^{[13
]}

Cabrera-Roldan, P. ^{[13
]}

Rodriguez-Melcon, J. I. ^{[1
,2
]}

Herrera-Ramos, E. ^{[14
,15
]}

Rodriguez-Gallego, C. ^{[14
]}

Lara, P. C. ^{[1
,2
,3
]}

机构：

[1] Hosp Univ Gran Canaria Dr Negrin, Dept Radiat Oncol, C Barranco Ballena S-N, Las Palmas Gran Canaria 35010, Las Palmas, Spain

[2] Inst Canario Invest Canc, Las Palmas Gran Canaria, Spain

[3] Univ Las Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain

[4] Hosp Esperanza, Dept Radiat Oncol, Inst Oncol Radioterap, Parc Salut Mar, Barcelona, Spain

[5] Univ Granada, Fac Med, Legal Med & Toxicol Dept, Lab Genet Identificat, Granada, Spain

[6] Pfizer Univ Granada, Andalusian Govt Ctr Genom & Oncol Res, GENYO, Granada, Spain

[7] Hosp Univ Virgen Nieves, Dept Urol, Granada, Spain

[8] Hosp Univ Bellvitge, Hosp Llobregat, Dept Urol, Barcelona, Spain

[9] Onkologikoa, Dept Radiat Oncol, Guipuzcoa, Spain

[10] Inst Recerca Hosp Mar IMIM, Hlth Serv Res Grp, Barcelona, Spain

[11] Hosp Llobregat, ICO, Dept Radiat Oncol, Barcelona, Spain

[12] Hosp Santa Creu & Sant Pau, Dept Radiat Oncol, Barcelona, Spain

[13] Hosp Univ Virgen Rocio, Dept Radiat Oncol, Seville, Spain

[14] Hosp Univ Gran Canaria Dr Negrin, Dept Immunol, Las Palmas Gran Canaria, Spain

[15] Univ Las Palmas Gran Canaria, Dept Med & Surg Sci, Las Palmas Gran Canaria, Spain

来源：

PROSTATE CANCER AND PROSTATIC DISEASES | 2016年 / 19卷 / 01期

关键词：

MAJOR VAULT PROTEIN; END-JOINING REPAIR; POLY(ADP-RIBOSE) POLYMERASE; DRUG-RESISTANCE; MVP EXPRESSION; RISK; SUSCEPTIBILITY; PREDICTION; INHIBITOR; PARP-1;

D O I：

10.1038/pcan.2015.63

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：28 / 34

页数：7

共 49 条

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