Influence of DPYD*9A, DPYD*6 and GSTP1 ile105val Genetic Polymorphisms on Capecitabine and Oxaliplatin (CAPOX) Associated Toxicities in Colorectal Cancer (CRC) Patients.
Autor: | Varma K A; Department of Pharmacology,JIPMER, Puducherry, India., Jayanthi M; Department of Pharmacology,JIPMER, Puducherry, India., Dubashi B; Department of Medical Oncology, JIPMER, Puducherry, India., Shewade DG; Department of Pharmacology,JIPMER, Puducherry, India. |
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Jazyk: | angličtina |
Zdroj: | Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2019 Oct 01; Vol. 20 (10), pp. 3093-3100. Date of Electronic Publication: 2019 Oct 01. |
DOI: | 10.31557/APJCP.2019.20.10.3093 |
Abstrakt: | Aim: CAPOX treatment in CRC patients was reported to cause several dose-limiting toxicities, and are found responsible for treatment interruption or even discontinuation. Therefore there is a critical need for identifying the predictive biomarkers for such toxicities to prevent them. The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and GSTP1 ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with CRC. Patients and Methods: We have recruited 145 newly diagnosed and treatment naive CRC patients in the study. Each Patient received a standard treatment schedule of oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. 5 ml of the venous blood was collected from each patient and genomic DNA extraction and genotyping. The genotyping analysis of the selected genetic polymorphisms was carried out by real-time PCR using TaqMan SNP genotyping assays obtained from applied biosystems. Results: The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9A carries were found to be at higher risk for HFS, diarrhoea and thrombocytopenia when compared to patients with wild allele. No significant association was found between DPYD*6, GSTP1 ile105val polymorphisms and CAPOX related toxicities except for thrombocytopenia. Conclusion: A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker. |
Databáze: | MEDLINE |
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