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Updated: Jul 8, 2025

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

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Developing DPYD Genotyping Method for Personalized Fluoropyrimidines Therapy.

Betty Y L Wong¹, Zhenyu Li², Michael Jonathon Raphael^3,4,5

¹Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

The Journal of Applied Laboratory Medicine

|December 12, 2023

Summary

This summary is machine-generated.

A new pharmacogenetic test accurately detects DPYD gene variants, identifying patients at high risk for severe toxicity from fluoropyrimidine chemotherapy. This assay aids in personalized treatment strategies for cancer patients.

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Published on: August 20, 2018

Area of Science:

Pharmacogenomics
Molecular Diagnostics
Oncology

Background:

Fluoropyrimidine drugs are essential chemotherapy agents for solid tumors.
Severe toxicity affects 10-40% of patients receiving fluoropyrimidine therapy.
DPYD gene variants impairing dihydropyrimidine dehydrogenase activity increase toxicity risk.

Purpose of the Study:

Develop a pharmacogenetic test to screen for DPYD variants.
Identify patients at increased risk of fluoropyrimidine-induced toxicity.
Guide personalized fluoropyrimidine therapy selection.

Main Methods:

Developed a multiplex allele-specific polymerase chain reaction (AS-PCR) assay.
Detected five common DPYD variants (c.557A > G, c.1129-5923C > G, c.1679T > G, c.1905 + 1G > A, c.2846A > T).
Validated the assay using population and proficiency testing samples, confirmed by Sanger sequencing.

Main Results:

Successfully detected DPYD variants in deidentified population and proficiency samples.
Assay demonstrated high concordance with Sanger sequencing for all tested variants.
Identified heterozygous carriers for key DPYD variants.

Conclusions:

A robust multiplex AS-PCR assay for rapid DPYD variant detection was established.
The test effectively screens for DPYD variants associated with fluoropyrimidine toxicity.
This assay supports personalized medicine by identifying at-risk patients for safer chemotherapy.