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XPG基因遗传变异与上皮性卵巢癌铂类化疗预后相关性研究

胡佩a康山a周荣秒b王娜b齐冰丽a李琰b   

  1. 作者单位: 河北医科大学第四医院,a.妇产科,b.分子生物学室,河北 石家庄 050011
  • 出版日期:2015-03-02 发布日期:2015-04-01
  • 通讯作者: 李琰
  • 基金资助:

    河北省自然基金(H2012206164)

The association between the polymorphisms of XPG tagSNPs and the clinical outcomes of epithelial ovarian cancer patients treated with platinum-based chemotherapy.

HU Pei**,KANG Shan**,ZHOU Rong-miaoWANG NaQI Bing-li**,LI Yan.   

  1. *Department of Gynaecology,Hebei Medical University,Fourth Hospital,Shijiazhuang 050011,China
  • Online:2015-03-02 Published:2015-04-01

摘要:

目的 探讨XPG基因单核苷酸多态性(SNPs)与上皮性卵巢癌铂类化疗预后的关系。方法 通过Haploview软件筛选出XPG基因9个标签SNPs(tagSNPs)。连接酶检测反应技术检测2002年3月至2009年12月在河北医科大学第四医院进行手术治疗的239例上皮性卵巢癌患者外周血DNA XPG基因9个tagSNPs的基因型频率分布情况。采用生存分析评估XPG基因SNPs与上皮性卵巢癌患者临床预后的关系。患者临床预后的判定指标包括患者对铂类化疗反应(TR)、疾病无进展生存期(PFS)和总生存期(OS)。结果 统计学分析显示:XPG基因rs1047768C/T和rs2296147C/T多态可能与确诊时年龄≥50岁的卵巢癌患者临床预后相关。即与rs1047768 T/T基因型相比,rs1047768C等位基因降低了患者铂类抵抗、疾病复发和死亡的风险(TR:OR=0.49,95%CI 0.24~0.98;PFS:HR=0.57,95%CI 0.38~0.87;OS:HR=0.56,95%CI 0.34~0.94);与rs2296147 T/T基因型相比,rs2296147C等位基因降低上皮性卵巢癌患者疾病复发和死亡的风险(PFS:HR=0.63,95%CI 0.41~0.98;OS:HR=0.50,95%CI 0.28~0.87)。结论 XPG rs1047768C/T和rs2296147C/T多态可能是确诊时年龄≥50岁卵巢癌患者临床预后的分子标志物。

关键词: XPG, tagSNPs, 上皮性卵巢癌, 铂类化疗, 临床预后

Abstract:

Abstract: Objective To investigate the association of XPG tagSNPs with susceptibility to the platinum chemotherapeutic treatment and survival in epithelial ovarian cancer (EOC) patients.Methods The case retrospective study included 239 ovarian cancer patients.We selected the tagSNPs of XPG gene in Chinese Han population inquired in Hapmap database,and possessed the minor allele frequency (MAF) ≥0.1.The nine tagSNPs (XPG rs1047768,rs2227869,rs4150387,rs17655,rs2296147,rs3759500,rs4150360,rs4150383 and rs751402) were genotyped by allelic specific multiple ligase detection reactions (LDR) method.The clinical outcome parameters included chemotherapy response (TR),progression-free survival (PFS) and overall survival (OS).Results The overall analysis showed that XPG tagSNPs were not associated with the clinical outcomes ovarian cancer.When stratified with the diagnosed age we found that XPGrs1047768C/T and rs2296147C/T polymorphisms were associated with clinical outcomes ovarian cancer patients.For rs1047768C/T polymorphism the C allele was associated with reducing chemotherapy response,PFS and OS in subjects that were older than 50 years of ages(of age TR,OR=0.49,95%CI 0.24~0.98;PFS,HR=0.57; 95% CI 0.38~0.87;OS,HR=0.56; 95%CI 0.34~0.94).Compared with the rs2296147T/T genotype,the C allele was associated with the PFS and OS (PFS,HR=0.63,95%CI 0.41~0.98;OS,HR=0.50; 95%CI 0.28~0.87).Conclusions The XPG rs1047768C/T and rs2296147C/T polymorphisms may play as the markers in predicting the clinical outcomes of ovarian cancer treated with platinum chemotherapy.

Key words: XPG;tagSNPs;epithelial ovarian cancer;platinum chemotherapy, clinical outcomes

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