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XRCC1基因多态性与卵巢癌对铂类药物化疗敏感性的相关性研究

成莉,李琳,邢辉   

  1. 湖北文理学院附属襄阳巿中心医院妇产科
  • 收稿日期:2013-12-17 修回日期:2014-02-12 出版日期:2014-04-30 发布日期:2014-04-30
  • 通讯作者: 邢辉

The correlation between single nucleotide polymorphism in XRCC1 and clinical response to platinum-based chemotherapy in ovarian cancer

CHENG Li, LI Lin, XING Hui.   

  1. Department of Gynaecology and Obstetrics, Center Hospital of Xiangyang of Hubei University of Arts and Science
  • Received:2013-12-17 Revised:2014-02-12 Online:2014-04-30 Published:2014-04-30
  • Contact: Xinghui

摘要: 目的 探讨X线修复交叉互补基因1(XRCC1)Arg194Trp和Arg399Gln位点多态性与卵巢癌对铂类药物化疗敏感性之间的关系。方法 选取82例首次术后以铂类为基础化疗达6个周期的卵巢癌患者,采用聚合酶链反应限制性片段长度多态性分析(PCRRFLP)检测外周血XRCC1 Arg194Trp和Arg399Gln位点的基因型,分别比较两个位点的不同基因型与化疗敏感性及两个位点之间的关系。
结果 XRCC1 Arg194Trp存在3个基因型,即Arg/Arg、Arg/Trp、Trp/Trp,基因分布频率分别为47.6%、43.9%、8.5%;XRCC1 Arg399Gln亦存在3个基因型,即Arg/Arg、Arg/Gln、Gln/Gln,基因分布频率分别为25.6%、40.2%、34.1%。XRCC1 Arg399Gln 的不同基因型在FIGO分期和年龄分组中的差异均有统计学意义(P<0.05)。化疗敏感组与不敏感组两个位点多态性基因型之间的差异均有统计学意义(P<0.05)。XRCC1 Arg194Trp的Trp/Trp和Arg 399Gln的Gln/Gln基因型比Arg/Arg基因型更易对铂类药物产生耐药性,比值比分别增加至13.50倍(95%CI:1.461~124.739)和7.65倍(95%CI:2.012~29.088)。同时携带Arg194Trp Arg/Trp和Arg399Gln Gln/Gln基因型的患者对化疗不敏感率高达84.62%(OR=22.00,95%CI:2.534~190.998;P<0.05)。结论 XRCC1 Arg194Trp和Arg399Gln位点基因多态性与卵巢癌对铂类药物的化疗敏感性相关,并且两位点之间存在联合效应。

Abstract: Objective To investigate the relationship between XRCC1 Arg194Trp and Arg399Gln polymorphism genotype and chemosensitivity to platinum-based in ovarian cancer.
Methods Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect 82 cases of XRCC1 Arg194Trp and Arg399Gln polymorphism genotype after platinumbased chemotherapy drugs up to six cycles of ovarian cancer. And the association between the two genes sites were analyzed.
Results XRCC1 Arg194Trp had three genotypes, namely Arg/Arg, Arg/Trp, Trp/Trp, and frequency distribution was 47.6%, 43.9%, 8.5%, respectively. XRCC1 Arg399Gln had three genotypes, namely Arg/Arg, Arg/Gln, Gln/Gln, and frequency distribution was 25.6%, 40.2%, 34.1%, respectively. There were statistically significant difference of different genotypes in FIGO stage and age group (P<0.05). The genotypes existed difference between the group of sensitive to chemotherapy and nonsensitive to chemotherapy (P<0.05). XRCC1 Arg194Trp Trp/Trp genotype and Arg399Gln Gln/Gln genotype were easier to resistance to platinum drug compared with the Arg/Arg genotype, the odds ratio could be increased by 13.50 (95%CI: 1.461-124.739) times and 7.65 (95%CI: 2.012-29.088) times, respectively. While carrying 194Arg/Trp and 399Gln/Gln patients have 84.62% of non-sensitive to chemotherapy(OR=22.00,95%CI:2.534~190.998;P<0.05). Conclusion Polymorphism in the XRCC1 Arg194Trp and Arg399Gln may have significant impact on the response of ovarian cancer to platinum-based chemotherapy; and the two gene sites have combined effect.

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