Henríquez-Hernández L A, Valenciano A, Foro-Arnalot P, Álvarez-Cubero M J, Cozar J M, Suárez-Novo J F, Castells-Esteve M, Fernández-Gonzalo P, De-Paula-Carranza B, Ferrer M, Guedea F, Sancho-Pardo G, Craven-Bartle J, Ortiz-Gordillo M J, Cabrera-Roldán P, Rodríguez-Melcón J I, Herrera-Ramos E, Rodríguez-Gallego C, Lara P C
Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain.
Instituto Canario de Investigación del Cáncer, Las Palmas, Spain.
Prostate Cancer Prostatic Dis. 2016 Mar;19(1):28-34. doi: 10.1038/pcan.2015.63. Epub 2016 Jan 12.
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.
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.
(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).
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.
为了更好地实现前列腺癌（PCa）治疗的个体化，需要新的前列腺癌预后和治疗反应预测指标。我们对494名西班牙前列腺癌患者检测了四个直接（XRCC5（中国仓鼠细胞X射线修复互补缺陷修复5）和XRCC6（中国仓鼠细胞X射线修复互补缺陷修复6））或间接（PARP1和主要穹窿蛋白（MVP））参与非同源末端连接的基因中的单核苷酸多态性（SNP）。
在Biotrove OpenArray NT循环仪中对总共22个SNP进行基因分型。获取了所有参与者的临床肿瘤分期、诊断时的PSA血清水平和Gleason评分。使用基于网络的SNPator环境确定基因型和等位基因频率。
（XRCC6）rs2267437表现为发生侵袭性更强的前列腺癌肿瘤的危险因素。与携带CC/CG基因型的患者相比，携带GG基因型的患者发生更大肿瘤的风险更高（优势比（OR）=2.04，95%置信区间（CI）1.26 - 3.29，P = 0.004），诊断时PSA水平更高（OR = 2.12，95%CI 1.19 - 3.78，P = 0.011），Gleason评分更高（OR = 1.65，95%CI 1.01 - 2.68，P = 0.044）以及D'Amico高风险肿瘤（OR = 2.38，95%CI 1.24 - 4.58，P = 0.009）。与携带CC基因型的患者相比，携带（MVP）rs3815824 TT基因型的患者诊断时PSA水平更高的风险更高（OR = 4.74，95%CI 1.40 - 16.07，P = 0.013）。当联合分析这两个SNP时，携带风险基因型的患者发生D'Amico高风险肿瘤的风险更高（OR = 3.33，95%CI 1.56 - 7.17，P = 0.002）。
我们认为，首次发现XRCC6和MVP基因的遗传变异与侵袭性更强疾病的风险相关，在评估前列腺癌的恶性程度时应予以考虑。
