University of Pittsburgh, Magee-Womens Hospital of UPMC, Pittsburgh PA, USA.
Gynecol Oncol. 2011 Jul;122(1):121-6. doi: 10.1016/j.ygyno.2011.03.027. Epub 2011 Apr 14.
This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy.
Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS).
The genotype distribution at codon 118 (n=278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT+TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR]=0.68, 95% confidence interval [CI]=0.49-0.95, p=0.025). The genotype distribution for C8092A in ERCC1 (N=280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA+AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR=1.29, 95% CI=0.97-1.72, p=0.077).
The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant.
本研究评估了切除修复交叉互补组 1（ERCC1）中与接受静脉注射卡铂和紫杉醇为基础的化疗的晚期上皮性卵巢/腹膜/输卵管癌（EOC/PPC/FTC）患者铂类诱导的 DNA 损伤修复相关的常见多态性。
采用焦磷酸测序法检测白细胞 DNA 中 ERCC1 密码子 118 和 C8092A 的单核苷酸多态性（SNP），这是妇科肿瘤学组 III 期 GOG-182 试验的一部分。采用 Kaplan-Meier 法和调整后的 Cox 回归模型来研究 ERCC1 多态性与无进展生存期（PFS）和总生存期（OS）之间的关系。
在 ERCC1 密码子 118 中（n=278），CC、CT 和 TT 的基因型分布分别为 23%、45%和 32%，中位 OS 分别为 32、47 和 43 个月。与 ERCC1 密码子 118 中的 CC 基因型相比，CT+TT 基因型的患者死亡风险降低（风险比[HR]=0.68，95%置信区间[CI]=0.49-0.95，p=0.025）。ERCC1 中 C8092A 的基因型分布（N=280）为 50%、42%和 8%，CC、CA 和 AA 的中位 OS 分别为 45、40 或 30 个月。与 ERCC1 中 C8092A 的 CC 基因型相比，CA+AA 基因型的患者死亡风险有增加的趋势（HR=1.29，95% CI=0.97-1.72，p=0.077）。
DNA 修复基因 ERCC1 密码子 118 的多态性是接受静脉注射卡铂和紫杉醇为基础的化疗的 EOC/PPC/FTC 患者生存的独立预测因素。ERCC1 中 C8092A 多态性与生存之间的关系较弱，其效应大小并不总是具有统计学意义。
