ERCC6 C6530G单核苷酸多态与局限期小细胞肺癌患者生存相关

Prediction of single nucleotide polymorphism in ERCC6 (C6530G) for the clinical outcome of limited small cell lung cancer

背景与目的：个体化治疗和靶向治疗是目前实体瘤治疗的两大发展方向。基因单核苷酸多态（SNP）不同基因型患者化疗疗效之间存在显著的差别，基因型与疗效之间的相关研究可能为实现个体化治疗提供重要的理论基础。已有研究证实DNA损伤修复基因ERCC1、XRCC1、XPD等基因的遗传变异与非小细胞肺癌铂类药物治疗的疗效及预后相关，尚无小细胞肺癌患者化疗疗效与损伤修复基因SNP相关研究的报告。本研究观察了ERCC6基因C6530G单核苷酸多态与局限期小细胞肺癌化疗近期疗效和生存的关系。方法：采用回顾性研究方法，分析了95例局限期小细胞肺癌患者经卡铂加VPl6（CE）方案一线或辅助治疗后的近期疗效及生存期与ERCC6 C6530GSNP的关系。ERCC6 C6530G基因型分析采用PCR—RFLP方法。组间比较采用卡方检验，生存分析采用Kaplan—Meier Log—rank检验法。结果：ERCC6 6530位点CC、CG和GG基因型患者的近期疗效分别为88．9％、90．3％和85．7％，差异无显著意义（P=1．0）。CG＋GG基因型患者中位TTP为13个月（95％CI=9．2～16．8），CC基因型患者中位1TrP为9个月（95％CI=7．3～10．6；P=0．19）。ERCC6 C6530GSNP和是否手术切除原发病灶两个因素与CE方案治疗后的生存期有关，其中CG＋GG基因型患者中位生存期为24个月（95％CI=18．4～29．6），CC基因型患者治疗后中位生存为16个月（95％CI=9．9～22．0），差异有显著性（P〈0．05）。手术切除原发病灶的患者中位生存期在中位随访时间28．5个月时尚未得到，未行手术切除的患者中位生存时间为18个月（95％CI 12．5～23．5），差异有显著性（P〈0．01）。结论：ERCC6 C6530GSNP与局限期小细胞肺癌患者CE方案近期疗效无关但与生存相关。ERCC6 C6530G基因型可能成为局限期小细胞肺癌患者化疗方案个体化选择的依据。

Background and purpose： Individualized treatment and target therapy are representative for the development of treatment of solid tumors. Patients with different SNP （single nucleotide polymorphism） genotypes response differently to chemotherapeutic agents. Correlation between genotype and chemotherapeutic response may become rationale how to design individualized treatment. DNA injury repair genes like ERCC1, XRCC1, XPD had been reported to associate with response rate of treatment and prognosis of non small cell lung cancer, but so far the role of the genes have not been well investigated in small cell lung cancer. Our research explores whether ERCC6 C6530G polymorphism is associated with treatment response and clinical outcome of small cell lung cancer （SCLC） after treated with carboplatin and etoposide （CE） regimen. Methods： In this retrospective study, 95 patients with limited stage SCLC were assessed for overall survival, response rate, and time to progression （TFP） according to ERCC6 C6530G genotypes, which were analyzed by PCR basedrestriction fragment length polymorphism （RFLP） assays. Chi-square test and single variant Kaplan-Meier, log-rank test were used to analyze data. All statistical tests were two-sided tests. Results： Response rate for patients with CC, CG and GG genotypes were 88.9%, 90.3% and 85.7% respectively （P = 1.0）. Median TFP for the CG ＋ GG and CC genotype groups were 13 months （95% CI = 9.2 - 16.8） and 9 months （95% CI = 7.3 - 10.6）. respectively（ P = 0.19）. ERCC6 C6530G genotypes and surgical reseetion were prognostic factors for SCLC patients treated with CE regimen. Patients with ERCC6 CG or GG genotype had a median survival of 24 months （95% CI = 18.4 -29.6） that was significantly longer than those with the CC genotype （ 16 month, 95% CI = 9.9 -22.0; P 〈0.05）. Median overall survival of patients underwent surgical resection did not be determined yet since median follow-up was only 28.5 months, but there was significantly longer than 18 month （95% CI = 12.5 -23.5） for patients without surgical resection in terms of median overall survival time（P 〈0. 01）. Conclusions： ERCC6 C6530G SNP might predict treatment outcome for the patients with SCLC treated with CE regimen. The patients with CG or GG genotype had better survival than one with the CC genotype. ERCC6 C6530G SNP might become rationale for individualized chemotherapy for SCLC patients.