[ERCC1基因多态性与上皮性卵巢癌患者铂类化疗疗效]

[Polymorphisms of ERCC1 gene and outcomes in epithelial ovarian cancer patients with platinum-based chemotherapy].

作者信息

Qi Bing-li, Li Yan, Wang Na, Zhou Rong-miao, Hu Pei, Kang Shan

机构信息

Department of Obstetrics and Gynecology, Forth Hospital, Hebei Medical University, Shijiazhuang 050011, China.

Email:

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2013 Nov;48(11):847-52.

PMID:24444563

Abstract

OBJECTIVE

To explore the relationship among single nucleotide polymorphism (SNP) of excision repair cross-complementing 1(ERCC1) gene, chemotherapy sensitivity and clinical outcomes of epithelial ovarian cancer (EOC) patients treated with platinum.

METHODS

Six tag single nucleotide polymorphisms (tagSNP;rs11615, rs3212986, rs735482, rs3212955, rs12610134 and rs3212958) were chose from ERCC1 gene. The genotypes of 6 tagSNP were determined by Snapshot method in 220 EOC patients. Primary clinical outcomes parameter contained EOC patients' responses to platinum-based chemotherapy, progression-free survival (PFS) and overall survival (OS) were analysed.

RESULTS

The rs11615 C/T SNP of ERCC1, CC, CT and TT genotype frequencies were 53.1%, 45.6%, 1.4% in responders to platinum-based chemotherapy, while 52.0%, 35.6%, 12.3% in non-responders, respectively, in which there was significant difference between the two groups (P = 0.002) . Compared with the patients with CC genotype, the patients carrying TT genotype had a significantly poor response to platinum-based chemotherapy (OR = 6.22, 95%CI:1.12-34.42). Similarly, the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was different between the recurrence and non-recurrence group, death and survival group (all P < 0.05). Kaplan-Meier survival analysis showed that the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was associated with PFS and OS (P < 0.01) of EOC patients. Cox's multivariate analysis suggested that patients with TT genotype had a shorter PFS (HR = 2.19, 95%CI:1.14-4.22, P = 0.009) and OS (HR = 2.22, 95%CI:1.06-4.64, P = 0.021) compared with those carrying CC genotype [adjusting for age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological type, grade and tumor residual size]. The genotypes frequencies distribution of rs3212986, rs735482, rs3212955, rs12610134 and rs3212958 SNP of ERCC1 did not show the significant difference between the responders to platinum-based chemotherapy and non-responders. The other 5 tagSNP may not be associated with the PFS and OS of EOC patients (all P > 0.05).

CONCLUSION

The rs11615 SNP of ERCC1 may become a valuable prognostic biomarker for EOC patients treated with platinum-based chemotherapy.

摘要

目的

探讨切除修复交叉互补基因1（ERCC1）单核苷酸多态性（SNP）与上皮性卵巢癌（EOC）患者铂类化疗敏感性及临床结局之间的关系。

方法

从ERCC1基因中选取6个标签单核苷酸多态性（tagSNP；rs11615、rs3212986、rs735482、rs3212955、rs12610134和rs3212958）。采用Snapshot法检测220例EOC患者6个tagSNP的基因型。分析主要临床结局参数，包括EOC患者对铂类化疗的反应、无进展生存期（PFS）和总生存期（OS）。

结果

ERCC1基因的rs11615 C/T SNP中，铂类化疗有效者的CC、CT和TT基因型频率分别为53.1%、45.6%、1.4%，而无效者分别为52.0%、35.6%、12.3%，两组间差异有统计学意义（P = 0.002）。与CC基因型患者相比携带TT基因型的患者对铂类化疗的反应明显较差（OR = 6.22，95%CI：1.12 - 34.42）。同样，ERCC1基因rs11615 C/T SNP的基因型频率分布在复发组与未复发组、死亡组与生存组之间存在差异（均P < ）。Kaplan-Meier生存分析显示，ERCC1基因rs11615 C/T SNP的基因型频率分布与EOC患者的PFS和OS相关（P < 0.01）。Cox多因素分析表明，与携带CC基因型的患者相比，TT基因型患者的PFS（HR = 2.19，95%CI：1.14 - 4.22，P = 0.009）和OS（HR = 2.22，95%CI：1.06 - 4.64，P = 0.021）较短[校正年龄、国际妇产科联盟（FIGO）分期、病理类型、分级和肿瘤残留大小]。ERCC1基因的rs3212986、rs735482、rs3212955、rs12610134和rs3212958 SNP的基因型频率分布在铂类化疗有效者与无效者之间未显示出显著差异。其他5个tagSNP可能与EOC患者的PFS和OS无关（均P > 0.05）。