Genetic Polymorphisms in Glutathione S-Transferase (GST) Gene and Their Correlation with Toxicity of Chemotherapy in Breast Cancer Patients

Document Type : Research Articles

Authors

1 Department of Oncology, Krishna Vishwa Vidyapeeth “Deemed to be University”, Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.

2 Department of Molecular Biology and Genetics, Krishna Institute of Allied Sciences, Krishna Vishwa Vidyapeeth “Deemed to be University”, Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.

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. Conclusion: 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. 

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Asian Pacific Journal of Cancer Prevention

Articles in Press, Accepted Manuscript
Available Online from 26 July 2024

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History

  • Receive Date: 20 September 2023
  • Revise Date: 30 March 2024
  • Accept Date: 13 July 2024

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