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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    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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History
  • Received:March 31,2013
  • Revised:May 13,2013
  • Adopted:June 19,2013
  • Online: August 20,2013
  • Published:
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