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
Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, 430085, China.
Cancer Med. 2016 Sep;5(9):2332-42. doi: 10.1002/cam4.822. Epub 2016 Jul 27.
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.
据报道，DNA修复可通过激活抗凋亡细胞防御机制赋予癌细胞对治疗的抗性。我们推测，DNA修复基因的遗传变异可能与肺癌预后相关。通过TaqMan分析对280例晚期非小细胞肺癌（NSCLC）患者中选自12个DNA修复基因的17个标签单核苷酸多态性（tagSNP）进行基因分型。研究了这些SNP与晚期NSCLC患者总生存期的相关性。携带ERCC2 rs50872 CT + TT基因型的晚期NSCLC患者比携带rs50872 CC基因型的患者具有显著更长的中位生存时间（MST）和更低的死亡风险[对数秩检验P = 0.031；校正后风险比（95%可信区间）= 0.73（0.55 - 0.98），P = 0.033]。这些效应主要见于较年轻患者（≤65岁）[风险比（95%可信区间）= 0.57（0.37 - 0.87），P = 0.010]、未接受手术的患者[风险比（95%可信区间）= 0.68（0.47 - 0.98），P = 0.036]但接受化疗的患者[风险比（95%可信区间）= 0.64（0.46 - 0.91），P = 0.012]或放疗的患者[风险比（95%可信区间）= 0.58（0.38 - 0.89），P = 0.013]。同时，与携带rs25487 GG基因型的晚期NSCLC患者相比，携带XRCC1 rs25487 GA + AA基因型的患者MST显著缩短（MST = 11.7对16.7，对数秩检验P = 0.048）。此外，与携带rs50872 CT + TT和rs25487 GG基因型（MST = 22.0个月）的患者相比，携带ERCC2 rs50872 CC与XRCC1 rs25487 GA + AA基因型组合的晚期NSCLC患者MST最短（11.2个月）且死亡风险最高[风险比（95%可信区间）= 1.70（1.15 - 2.52），P = 0.008]。在中国人群中，ERCC2 rs50872的T等位基因与晚期NSCLC患者的良好生存相关，但XRCC1 rs25487的A等位基因与不良生存相关，这可能为预测临床结局提供新的生物标志物。
