ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.
ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.
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ERCC1 Cys8092Ala 和 XRCC1 Arg399Gln 多态性预测鼻咽癌根治性放射治疗后的无进展生存期
DOI：
10.1371/journal.pone.0101256
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Jin H;Xie X;Wang H;Hu J;Liu F;Liu Z;Zhou J;Zhang Y;Xi X;Hu B;Liao Y;Tang J
DNA修复基因中的单核苷酸多态性（SNP）可以改变基因表达和活性，并影响对癌症治疗的反应，从而影响生存率。本研究旨在评估XRCC 1 Arg 399 Gln和ERCC 1 Cys 8092 Ala单核苷酸多态性的效用，在治疗前活检样本中测量，作为非转移性鼻咽癌（NPC）患者对放疗反应的预测因子。材料与方法75例II-IVA-B期鼻咽癌患者。通过桑格测序从石蜡包埋的活检标本中鉴定XRCC 1 Arg 399 Glu和ERCC 1 Cys 8092 Ala SNP。免疫组织化学染色分析p53和pAkt蛋白的表达。采用考克斯比例风险模型、Kaplan-Meier法和对数秩检验分析遗传多态性与无进展生存期（PFS）之间的潜在关系。结果多因素分析显示ERCC 1 8092 Ala/Ala基因型携带者[风险比（HR）1.882; 95%可信区间（CI）1.031-3.438; P = 0.039]和XRCC 1 Arg/Arg基因型携带者（HR 2.019; 95%CI 1.010-4.036; P = 0.047）重度吸烟者（≥20包-年）的PFS率显著降低。 此外，p53和pAkt的联合阳性表达导致携带XRCC 1 Gln等位基因（HR 7.057; 95% CI 2.073-24.021; P = 0.002）或ERCC 1 Cys等位基因（HR 2.568; 95% CI 1.056-6.248; P = 0.038）的亚组的PFS显著增加。 结论ERCC 1基因Cys 8092 Ala多态性是鼻咽癌放疗疗效的独立预测因子，XRCC 1基因Arg 399 Glu突变联合吸烟状态可能是鼻咽癌无进展生存的预测因子。我们的研究结果进一步表明，这些基因多态性和p53蛋白的生存状态之间可能存在相关性。
Background Single nucleotide polymorphisms (SNPs) in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC). Materials and methods The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS) were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test. Results Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR) 1.882; 95% confidence interval (CI) 1.031–3.438; P = 0.039] and heavy smokers (≥20 pack-years) carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010–4.036; P = 0.047) had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073–24.021; P = 0.002) or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056–6.248; P = 0.038). Conclusions The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.
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影响因子：
3
作者：
Chen, Cui;Wang, Fenghua;Li, Yuhong
通讯作者：
Li, Yuhong
影响因子：
4.3
作者：
Salles, B;Sattler, U;Calsou, P
通讯作者：
Calsou, P
影响因子：
3
作者：
Monaco, Regina;Rosal, Ramon;Brandt-Rauf, Paul W.
通讯作者：
Brandt-Rauf, Paul W.
影响因子：
45.3
作者：
Quintela-Fandino, Miguel;Hitt, Ricardo;Sanchez-Cespedes, Montserrat
通讯作者：
Sanchez-Cespedes, Montserrat
影响因子：
6.4
作者：
Pastorelli, R;Cerri, A;Airoldi, L
通讯作者：
Airoldi, L