谷胱甘肽转硫酶P1(rs1695)基因多态性与Ⅳ期乳腺癌紫杉类和(或)蒽环类药物化疗疗效的关系
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宁夏回族自治区银川市应用研究开发计划项目(2011029).


Association of polymorphisms of GSTP1(rs1695) with the efficacy of paclitaxel/anthracycline-based chemotherapy in stage Ⅳ breast cancer
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Supported by Yinchuan Applied Research and Development Project of Ningxia Hui Autonomous Region (2011029).

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    摘要:

    目的 检测乳腺癌患者外周血谷胱甘肽转硫酶P1(glutathione S-transferase P1,GSTP1) 单核苷酸多态性位点rs1695\[GSTP1 (rs1695)\]的基因分型,分析其与Ⅳ期乳腺癌患者采用紫杉类和(或)蒽环类药物化疗疗效的关系。方法 应用聚合酶链式反应(PCR)-高分辨率熔解曲线技术(high resolution melting,HRM)检测128例Ⅳ期女性乳腺癌患者外周血中GSTP1(rs1695)基因分型,并根据PCR-HRM检测的不同基因型随机抽取10%的样本进行测序验证。应用SPSS 11.5软件进行统计学分析,采用Hardy-Weinberg遗传平衡检验方法进行基因型分布遗传平衡吻合度检验,采用χ2检验及Fisher确切概率法分析不同基因型与乳腺癌患者化疗疗效的关系,用非条件logistic回归模型计算比值比(OR)和95%可信区间(CI)。结果 128例Ⅳ期乳腺癌患者中,GSTP1(rs1695)AA基因型占57.8%(74/128)、AG基因型占39.8%(51/128)、GG基因型占2.3%(3/128),经Hardy-Weinberg遗传平衡检验,证实本研究入组病例GSTP1(rs1695)基因具有群体代表性(P>0.05)。128例患者均接受以紫杉类和(或)蒽环类药物为基础的化疗方案,化疗有效率为57.03%(73/128),化疗无效率为42.97%(55/128),化疗无效病例中病情稳定占18.75%(24/128),AG/GG基因型患者的化疗疗效优于AA基因型(OR=4.139, 95%CI:1.907~8.975,P<0.01),携带G基因患者的化疗有效率高于携带A基因的患者(χ2=12.163,P<0.01);其中70例紫杉类联合蒽环类药物化疗的患者中,AG/GG基因型患者的化疗疗效优于AA基因型(OR=4.016, 95%CI:1.404~11.483,P<0.01),携带G基因患者的化疗有效率高于携带A基因的患者(χ2=5.943,P<0.05)。结论 GSTP1(rs1695)的基因多态性可作为乳腺癌患者采用紫杉类和(或)蒽环类药物化疗疗效预测的遗传标记物,值得进一步大样本量的研究。

    Abstract:

    Objective To detect the single nucleotide polymorphisms of rs1695 of glutathione S-transferase P1\[GSTP1 (rs1695)\] in the peripheral blood of breast cancer patients, and to analyze its association with the efficacy of paclitaxel/anthracycline-based chemotherapy in stage Ⅳ breast cancer patients. Methods The genotypes of GSTP1 (rs1695) gene polymorphisms were determined by polymerase chain reaction (PCR)-high resolution melting (HRM) method in 128 cases of female stage Ⅳ breast cancer, and 10% samples were tested by gene sequencing technique according to the PCR-HRM results. The SPSS 11.5 software was used for statistical analysis, the Hardy-Weinberg equilibrium test was used for genetic equilibrium distribution of genotypes, the correlation of different genotypes with chemotherapy responses was analyzed by the χ2 test and Fisher’s exact test, and non-conditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI). Results Of the 128 cases of stage Ⅳ breast cancer, GSTP1(rs1695) AA genotype accounted for 57.8% (74/128), AG genotype for 39.8%(51/128), and GG genotype for 2.3%(3/128). Hardy-Weinberg test suggested that our research had a group representation (P>0.05). Chemotherapy with paclitaxel/anthracycline yielded an efficiency rate of 57.03% (73/128) and an inefficiency rate of 42.97% (55/128), and in the latter the stable disease accounted for 18.75% (24/128). Patients carrying GSTP1 (rs1695) AG/GG genotype had a better response to chemotherapy than those carrying AA genotype (OR=4.139, 95%CI:1.907-8.975,P<0.01), and GSTP1(rs1695) G gene carriers had a better response than A gene carriers (χ2=12.163,P<0.01). Among the 70 cases receiving combined treatment with anthracycline, those carrying GSTP1 (rs1695) AG/GG genotype had a better response than those carrying AA genotype (OR=4.016, 95%CI:1.404-11.483, P<0.01), and GSTP1(rs1695) G gene carriers had a better response than A gene carriers (χ2=5.943,P<0.05). Conclusion Genetic polymorphisms in GSTP1 (rs1695) can serve as a genetic marker to forecast the chemotherapy response of stage Ⅳ breast cancer patients to paclitaxel/anthracycline-based chemotherapy, which is worthy of further large sample study.

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  • 收稿日期:2013-03-31
  • 最后修改日期:2013-05-13
  • 录用日期:2013-06-19
  • 在线发布日期: 2013-08-20
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