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.
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。