The genetic variations in DNA repair genes ERCC2 and XRCC1 were associated with the overall survival of advanced non-small-cell lung cancer patients.
The genetic variations in DNA repair genes ERCC2 and XRCC1 were associated with the overall survival of advanced non-small-cell lung cancer patients.
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DOI：
10.1002/cam4.822
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发表时间：
2016-09
期刊：
影响因子：
4
通讯作者：
Guo, Huan
中科院分区：
文献类型：
--
作者：
Wang, Suhan;Wang, Jianzhong;Bai, Yansen;Wang, Qing;Liu, Li;Zhang, Kai;Hong, Xiaohua;Deng, Qifei;Zhang, Xiaomin;He, Meian;Wu, Tangchun;Xu, Ping;Guo, Huan
据报道，DNA修复可以通过激活抗凋亡细胞防御来赋予癌细胞对治疗性治疗的抗性。我们推测DNA修复基因的遗传变异可能与肺癌预后有关。采用TaqMan法对280例晚期非小细胞肺癌（NSCLC）患者的12个DNA修复基因中的17个标记单核苷酸多态性（tagSNPs）进行基因分型。研究这些SNP与晚期NSCLC患者总生存率的关系。携带ERCC 2 rs 50872 CT+TT基因型的晚期NSCLC患者的中位生存时间（MST）显著长于rs 50872 CC基因型患者，死亡风险显著降低[对数秩P = 0.031;校正HR（95% CI）= 0.73（0.55-0.98），P = 0.033]。这些影响主要见于年轻患者（≤65岁）[HR（95% CI）= 0.57（0.37-0.87），P = 0.010]，未手术患者[HR（95% CI）= 0.68（0.47-0.98），P = 0.036]，而化疗[HR（95%CI）= 0.64（0.46-0.91），P = 0.012]或放疗[HR（95%CI）= 0.58（0.38-0.89），P = 0.013]。同时，与携带rs 25487 GG基因型的晚期NSCLC患者相比，携带XRCC 1 rs 25487 GA+AA基因型的患者的MST显著更短（MST = 11.7 vs. 16.7，对数秩P = 0.048）。此外，携带ERCC 2 rs 50872 CC联合XRCC 1 rs 25487 GA+AA基因型的晚期NSCLC患者的MST最短，（11.2个月）和最高死亡风险[HR（95% CI）= 1.70（1.15-2.52），P = 0.008]与携带rs 50872 CT+TT和rs 25487 GG基因型的对照组比较（MST = 22.0个月）。ERCC 2 rs 50872 T等位基因与中国人群中晚期NSCLC患者的生存率相关，而XRCC 1 rs 25487 A等位基因与中国人群中晚期NSCLC患者的生存率相关。
It was reported that DNA repair can confer cancer cell resistance to therapeutic treatments by activating antiapoptotic cellular defense. We hypothesized that genetic variants of DNA repair genes may be associated with lung cancer prognosis. Seventeen tagging single‐nucleotide polymorphism (tagSNPs) selected from 12 DNA repair genes were genotyped in 280 advanced non‐small‐cell lung cancer (NSCLC) patients by TaqMan assay. The associations of these SNPs and overall survival of advanced NSCLC patients were investigated. Advanced NSCLC patients carrying ERCC2 rs50872 CT+TT genotypes had significantly longer median survival time (MST) and decreased death risk than patients with rs50872 CC genotype [log‐rank P = 0.031; adjusted HR(95% CI) = 0.73 (0.55–0.98), P = 0.033]. These effects were mainly seen among younger patients (≤65 years old) [HR(95% CI) = 0.57 (0.37–0.87), P = 0.010], patients without surgery [HR(95% CI) = 0.68 (0.47–0.98), P = 0.036] but with chemotherapy [HR(95% CI) = 0.64 (0.46–0.91), P = 0.012] or radiotherapy [HR(95% CI) = 0.58 (0.38–0.89), P = 0.013]. Meanwhile, compared to advanced NSCLC patients with rs25487 GG genotype, patients carrying XRCC1 rs25487 GA+AA genotypes had significantly shorter MST (MST = 11.7 vs. 16.7, log‐rank P = 0.048). In addition, advanced NSCLC patients carrying the ERCC2 rs50872 CC in combination with XRCC1 rs25487 GA+AA genotype had the shortest MST (11.2 month) and highest death risk [HR(95% CI) = 1.70 (1.15–2.52), P = 0.008] when compared with those carrying rs50872 CT+TT and rs25487 GG genotype (MST = 22.0 month). The ERCC2 rs50872 T allele was associated with favorable but XRCC1 rs25487 A allele with bad survival for advanced NSCLC in Chinese population, which may offer novel biomarkers for predicting clinical outcomes.
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影响因子：
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作者：
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