Abstract：
BACKGROUND: Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients.
METHODS: Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis.
RESULTS: After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy.
CONCLUSIONS: The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.
METHODS: Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis.
RESULTS: After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy.
CONCLUSIONS: The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.
摘要：
背景：谷胱甘肽S-转移酶（GST）是II期代谢酶家族，有助于解毒和消除各种内源性和外源性异种物质，包括化疗剂。有关GST）酶编码基因遗传多态性影响的全面知识将有助于了解阿霉素或紫杉醇或两者联合治疗的乳腺癌患者的临床结局。在这项研究中，我们试图评估乳腺癌患者GSTM1，GSTT1，GSTP1的遗传多态性及其与阿霉素和紫杉醇诱导的毒性反应的关系。
方法：本研究纳入接受阿霉素和紫杉醇化疗的200例BC患者，观察化疗引起的血液学和非血液学毒性反应。通过PCR和RFLP分析研究了GSTM1，GSTP1和GSTT1基因的多态性。
结果：在对GSTM1，GSTP1和GSTT1的遗传多态性进行单因素分析后，GSTT1无效基因型与中性粒细胞减少显着相关（OR=2.84，95％CI：1.06-7.56；p=0.036）在接受阿霉素治疗的乳腺癌患者和GSTT1无效基因型>1CINV的患者中，证实了显着相关性（OR=0.005-59在接受紫杉醇化疗的乳腺癌患者中，GSTP1（外显子5）A/G杂合基因型的遗传多态性在黏膜炎的>1级毒性反应中具有显着意义（OR=3.22，95％CI：1.06-9.71；p=0.037）。
结论：从这项研究中获得的发现表明，GSTT1-null基因型在响应阿霉素的血液中性粒细胞减少症毒性中的显着参与，而GSTM1-null基因型与响应的非血液毒性（身体疼痛）呈负相关紫杉醇。
方法：本研究纳入接受阿霉素和紫杉醇化疗的200例BC患者，观察化疗引起的血液学和非血液学毒性反应。通过PCR和RFLP分析研究了GSTM1，GSTP1和GSTT1基因的多态性。
结果：在对GSTM1，GSTP1和GSTT1的遗传多态性进行单因素分析后，GSTT1无效基因型与中性粒细胞减少显着相关（OR=2.84，95％CI：1.06-7.56；p=0.036）在接受阿霉素治疗的乳腺癌患者和GSTT1无效基因型>1CINV的患者中，证实了显着相关性（OR=0.005-59在接受紫杉醇化疗的乳腺癌患者中，GSTP1（外显子5）A/G杂合基因型的遗传多态性在黏膜炎的>1级毒性反应中具有显着意义（OR=3.22，95％CI：1.06-9.71；p=0.037）。
结论：从这项研究中获得的发现表明，GSTT1-null基因型在响应阿霉素的血液中性粒细胞减少症毒性中的显着参与，而GSTM1-null基因型与响应的非血液毒性（身体疼痛）呈负相关紫杉醇。
