Influence of DPYD*9A, DPYD*6 and GSTP1 ile105val Genetic Polymorphisms on Capecitabine and Oxaliplatin (CAPOX) Associated Toxicities in Colorectal Cancer (CRC) Patients

Document Type: Research Articles

Authors

1 Department of Pharmacology,JIPMER, Puducherry, India.

2 Department of Medical Oncology, JIPMER, Puducherry, India.

Abstract

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.

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