Related Experiment Video
Updated: Nov 27, 2025
qPCRTag Analysis - A High Throughput, Real Time PCR Assay for Sc2.0 Genotyping
Published on: May 25, 2015
Implementing DPYD*2A Genotyping in Clinical Practice: The Quebec, Canada, Experience
Catherine Jolivet1, Rami Nassabein1, Denis Soulières1
1Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.
Background:
Fluoropyrimidines are used in chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. DPYD*2A polymorphism is one of the most studied variants. The study objective was to document the impact of implementing this test in routine clinical practice.
Methods:
We retrospectively performed chart reviews of all patients who tested positive for a heterozygous or homozygous DPYD*2A mutation in samples obtained from patients throughout the province of Quebec, Canada.
Results:
During a period of 17 months, 2,617 patients were tested: 25 patients tested positive. All were White. Twenty-four of the 25 patients were heterozygous (0.92%), and one was homozygous (0.038%). Data were available for 20 patients: 15 were tested upfront, whereas five were identified after severe toxicities. Of the five patients confirmed after toxicities, all had grade 4 cytopenias, 80% grade ≥3 mucositis, 20% grade 3 rash, and 20% grade 3 diarrhea. Eight patients identified with DPYD*2A mutation prior to treatment received fluoropyrimidine-based chemotherapy at reduced initial doses. The average fluoropyrimidine dose intensity during chemotherapy was 50%. No grade ≥3 toxicities were observed. DPYD*2A test results were available in an average of 6 days, causing no significant delays in treatment initiation.
Conclusion:
Upfront genotyping before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation. The administration of chemotherapy at reduced doses appears to be safe in patients heterozygous for DPYD*2A.
Implications For Practice:
Fluoropyrimidines are part of chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. This retrospective analysis demonstrates that upfront genotyping of DPYD before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation. This approach was reported previously, but insufficient data concerning its application in real practice are available. This is likely the first reported experience of systematic DPYD genotyping all over Canada and North America as well.
Insights
Implementing DPYD*2A genetic testing before chemotherapy can prevent severe toxicities. This DPYD genotyping is feasible in routine practice, ensuring safe reduced chemotherapy doses for patients with DPYD mutations.
Area of Science:
- Pharmacogenomics
- Clinical Chemistry
- Oncology
Background:
- Fluoropyrimidines are crucial in combination cancer chemotherapy.
- Dihydropyrimidine dehydrogenase (DPD) deficiency can cause severe, life-threatening toxicities.
- The DPYD*2A polymorphism is a well-studied genetic variant associated with DPD deficiency.
Purpose of the Study:
- To evaluate the impact of integrating DPYD*2A genetic testing into routine clinical practice.
- To assess the feasibility and outcomes of upfront DPYD genotyping before fluoropyrimidine-based chemotherapy.
Main Methods:
- Retrospective chart review of patients with heterozygous or homozygous DPYD*2A mutations in Quebec, Canada.
- Analysis of DPYD*2A testing results and subsequent clinical outcomes over a 17-month period.
- Comparison of outcomes between patients tested upfront versus those identified after experiencing toxicities.
Main Results:
- Out of 2,617 patients tested, 25 (0.95%) had a DPYD*2A mutation (24 heterozygous, 1 homozygous), all of White ethnicity.
- Fifteen patients received upfront DPYD testing, while five were identified post-toxicity.
- Patients receiving reduced chemotherapy doses based on upfront DPYD*2A testing experienced no severe toxicities (grade ≥3).
- DPYD*2A test results were available within an average of 6 days, without delaying treatment initiation.
Conclusions:
- Upfront DPYD genotyping is a feasible strategy in clinical practice to prevent severe toxicities and hospitalizations.
- Administering fluoropyrimidine chemotherapy at reduced doses is safe for patients heterozygous for the DPYD*2A mutation.
- Systematic DPYD genotyping before treatment can optimize cancer therapy and patient safety.
