Huang Xue, Liu Changmin, Cui Yayun, Zhang Heping, Liu Yongping, Zhou Xifa, Luo Judong
Department of Radiation Oncology, Changzhou Tumor Hospital Affiliated to Soochow University, Changzhou, Jiangsu 213001, P.R. China.
Department of Oncology, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, P.R. China.
Oncol Lett. 2017 Feb;13(2):704-714. doi: 10.3892/ol.2016.5496. Epub 2016 Dec 14.
The aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in X-ray repair cross-complementing 1-399 (XRCC1-399) or excision repair cross-complementation group 1-118 (ERCC1-118) and the short-term efficacy of radiochemotherapy, tumor metastasis and relapse, as well as the survival time in patients with esophageal squamous cell carcinoma (ESCC). TaqMan probe-based quantitative polymerase chain reaction (qPCR) was conducted to examine the levels of XRCC1-399 and ERCC1-118 SNPs in the peripheral blood of 50 patients with pathologically confirmed ESCC. In addition, the associations between different genotypes and short-term therapeutic efficacy [the complete remission (CR) rate], tumor metastasis and relapse, as well as the survival time following concurrent radiochemotherapy, were determined. A total of 50 ESCC patients who received concurrent radiochemotherapy were enrolled. It was found that the short-term therapeutic efficacy (CR rate) was higher in the group of patients carrying the homozygous mutation of XRCC1-399 (A/A genotype) than in the group of patients without the XRCC1-399 mutation (G/G genotype). In addition, the CR rate was significantly increased in patients carrying one or two ERCC1-118 C alleles (C/C or C/T genotype) compared with patients lacking the C allele (T/T genotype). The differences were statistically significant (A/A vs. G/G, P=0.014; TT vs. C/T+C/C, P=0.040). During the follow-up period, the group of patients carrying the homozygous mutation of XRCC1-399 (A/A genotype) exhibited a markedly reduced risk of metastasis and relapse compared with the group of patients carrying non-mutated XRCC1-399 (G/G genotype; P=0.031). By contrast, ERCC1-118 SNP was not associated with the risk of metastasis and recurrence (P>0.05). The combined results of univariate and multivariate Cox regression analysis showed that the SNP in ERCC1-118 was closely associated with survival time. The mean survival time was significantly prolonged in patients carrying 1 or 2 C alleles (C/C or C/T genotype) compared with patients lacking the C allele (T/T genotype) [T/T vs. C/C, HR=12.96, 95% confidence interval (CI)=3.08-54.61, P<0.001; TT vs. C/T+C/C, HR=11.71, 95% CI=3.06-44.83, P<0.001]. However, XRCC1-399SNP had no effect on survival time (P>0.05). XRCCl-399 SNP was associated with the short-term therapeutic efficacy (the CR rate) and tumor metastasis/relapse in ESCC patients who received the docetaxel plus cisplatin (TP) regimen-based concurrent radiochemotherapy. By contrast, ERCC1-118 SNP was significantly associated with the short-term therapeutic efficacy (the CR rate) and survival time in ESCC patients who received TP regimen-based concurrent radiochemotherapy.
本研究旨在探讨X射线修复交叉互补蛋白1 - 399（XRCC1 - 399）或切除修复交叉互补基因1 - 118（ERCC1 - 118）中的单核苷酸多态性（SNP）与食管鳞状细胞癌（ESCC）患者放化疗的短期疗效、肿瘤转移和复发以及生存时间之间的关联。采用基于TaqMan探针的定量聚合酶链反应（qPCR）检测50例经病理确诊的ESCC患者外周血中XRCC1 - 399和ERCC1 - 118 SNP的水平。此外，还确定了不同基因型与短期治疗疗效[完全缓解（CR）率]、肿瘤转移和复发以及同步放化疗后生存时间之间的关联。共纳入50例接受同步放化疗的ESCC患者。结果发现，携带XRCC1 - 399纯合突变（A/A基因型）的患者组短期治疗疗效（CR率）高于未发生XRCC1 - 399突变的患者组（G/G基因型）。此外，与缺乏C等位基因（T/T基因型）的患者相比，携带1个或2个ERCC1 - 118 C等位基因（C/C或C/T基因型）的患者CR率显著升高。差异具有统计学意义（A/A与G/G，P = 0.014；TT与C/T + C/C，P = 0.040）。在随访期间，携带XRCC1 - 399纯合突变（A/A基因型）的患者组与携带未突变XRCC1 - 399（G/G基因型）的患者组相比，转移和复发风险显著降低（P = 0.031）。相比之下，ERCC1 - 118 SNP与转移和复发风险无关（P>0.05）。单因素和多因素Cox回归分析的综合结果显示，ERCC1 - 118中的SNP与生存时间密切相关。与缺乏C等位基因（T/T基因型）的患者相比，携带1个或2个C等位基因（C/C或C/T基因型）的患者平均生存时间显著延长[T/T与C/C，风险比（HR）= 12.96，95%置信区间（CI）= 3.08 - 54.61，P<0.001；TT与C/T + C/C，HR = 11.71，95% CI = 3.06 -
