DPyD Polymorphism: Are Indians Different? A Single-Center Experience
Year: 2026
Type: article
Study design: Observational Study
Abstract: Aims and Objectives: Mutations of DPyD can result in severe adverse reactions and even death in patients receiving fluoropyrimidines, a common chemotherapeutic agent. The spectrum of mutations and their clinical significance in Indians is not well characterized to date; resulting in unexpected toxicity in many patients. To describe the spectrum of DPyD mutations in the screened population. To find causal associations between mutations and possible Treatment Related Adverse Events (TRAE). Materials and Methods: A Prospective analysis of GI cancer patients who were tested for DPyD deficiency between January 1, 2023 to July 30, 2024, for a period of 4 chemotherapy cycles. The incidence of TRAEs were noted and correlated with DPyD screening result. Results: Of the 169 cases screened, 150 were analyzed of whom toxicity (any grade) was seen in 54 (36%) patients [Grade III/IV toxicity-20 (13.3%), death-5 (3 in DPD wild type and 2 mutation positive)]. Twenty required hospitalization. Pre-emptive testing was done in 133 and for 17 after toxicity. Mutations were detected in 109 cases (64.4%) of which 34 (22.6%) patients had TRAEs -any grade and 12 - grade III/IV - including 2 deaths (both were poor metabolizers with loos of function mutation). In the remaining 41 wild-type patients, 20 (13.3%) had toxicity (any grade) and 8 (5.3%) - grade III/IV- including 3 deaths. The most common mutation was c. 85T>C DPYD*9A p.C29R ( n = 50) followed by c.2194G>A DPYD*6 p.V732I ( n = 22) of whom 40% and 50% had toxicity which did not correlate with CPIC recommendations except in 2 cases. Two patients had non-functional mutations causing death in both. Conclusion: The spectrum of DPyD mutations in our study seemed different from the Dutch and CPIC databases. The toxicity did not correlate with CPIC recommendations, needing an entirely different dose modification guideline for Indian population. Publication History Article published online: 20 February 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Institution: Meenakshi Mission Hospital and Research Centre
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7130700115