Cancer genetics - pre-treatment safety
DPYD Testing
A pre-treatment genetic safety screen for patients about to receive fluoropyrimidine chemotherapy. Identifies DPYD variants that cause severe and potentially fatal drug toxicity before the first dose is given.
Pre-treatment safety screen
Blood sample
5-FU and capecitabine
Clinician-ordered
Overview
What this test is
Fluoropyrimidine chemotherapy is among the most widely used cancer treatments in the world. In patients with DPYD variants that impair drug metabolism, standard doses can cause life-threatening toxicity. This test identifies those patients before treatment begins.
DPYD encodes dihydropyrimidine dehydrogenase, the enzyme responsible for metabolising fluoropyrimidine drugs including 5-fluorouracil (5-FU) and capecitabine. Patients who carry loss-of-function variants in DPYD cannot break down these drugs at a normal rate, causing toxic accumulation that can result in severe mucositis, myelosuppression, neurotoxicity, and death. DPYD testing identifies a patient’s metaboliser status before chemotherapy is initiated, enabling dose adjustment or alternative treatment selection to prevent serious harm.
1 in 20
patients carry a DPYD variant affecting fluoropyrimidine metabolism
5-FU
one of the most prescribed chemotherapy agents globally
CPIC
guidelines recommend pre-treatment DPYD genotyping before fluoropyrimidine therapy
Fatal
toxicity risk in poor metabolisers receiving standard fluoropyrimidine doses
Affected drugs
Fluoropyrimidines requiring DPYD screening
DPYD variants affect the metabolism of all fluoropyrimidine agents. The two most clinically significant are:
5-Fluorouracil (5-FU)
Intravenous fluoropyrimidine
One of the most widely used chemotherapy agents in oncology. Administered intravenously, often as part of combination regimens. In DPYD poor metabolisers, standard infusion doses carry a significantly elevated risk of grade 3 to 4 toxicity and treatment-related death.
Capecitabine (Xeloda)
Oral fluoropyrimidine prodrug
An oral prodrug that is converted to 5-FU in the body. Widely used as a more convenient alternative to intravenous 5-FU. DPYD variant carriers receiving capecitabine face the same toxicity risks as those receiving intravenous 5-FU and require the same pre-treatment screening.
Metaboliser phenotypes
What DPYD status means clinically
DPYD genotyping assigns a metaboliser phenotype that directly informs dose management. There are three possible outcomes.
Two non-functional DPYD alleles. Standard fluoropyrimidine dosing is contraindicated. Alternative therapy should be considered.
One non-functional or reduced activity allele. CPIC guidelines recommend a 25 to 50% starting dose reduction with careful monitoring.
No clinically significant DPYD variants detected. Standard fluoropyrimidine dosing is appropriate based on genetic status.
How it works
From referral to result
01
Clinician referral
Testing is ordered by the treating oncologist or prescribing clinician before fluoropyrimidine chemotherapy is initiated. DPYD testing should be requested as early as possible in the treatment planning process to avoid delays to chemotherapy start.
02
Blood sample collection
A blood sample collected in an EDTA tube by one of our registered phlebotomists, arranged at a time and location convenient to the patient. No special preparation is required.
03
Genotyping and analysis
The sample is processed in our South African laboratory. DPYD variants are identified and assigned a metaboliser phenotype in accordance with CPIC and DPWG guidelines.
03
Result and clinical briefing
Results are reported directly to the referring clinician with dosing guidance aligned to CPIC recommendations. A Genetix geneticist is available to discuss findings directly with your team where required.
Sample requirements
What we need
Sample type
Blood collected in an EDTA tube by one of our registered phlebotomists
Turnaround
Results typically available within 5 to 7 working days of sample receipt. Verify with the laboratory before requesting.
Collection
At a time and location convenient to the patient. We come to you.
Your result
What the report tells you
Results are reported to the referring clinician and include genotype, phenotype assignment, and dosing guidance aligned to current international guidelines.
01
DPYD genotype
Identification of clinically significant DPYD variants screened across the key pharmacogenomically relevant positions, including DPYD*2A, DPYD*3, DPYD*4, DPYD*5, DPYD*6, DPYD*7, DPYD*8, DPYD*9A, DPYD*9B, DPYD*10, DPYD*11, DPYD*12, DPYD*13, HapB3, rs115232898 (“African variant”), rs72549310, rs67376798, rs72549309, rs75017182.
02
Metaboliser phenotype
A clear phenotype assignment - poor, intermediate, or normal - based on detected genotype and in accordance with CPIC activity score methodology.
03
Dosing guidance
Actionable dosing recommendations aligned to CPIC and DPWG guidelines, including specific dose reduction recommendations for intermediate metabolisers and contraindication guidance for poor metabolisers.
Results are reported directly to the referring clinician.
A Genetix geneticist reviews findings with your team before the report is finalised. Dosing decisions remain the clinical responsibility of the treating oncologist. Your patient's report is released only once you have authorised it.
Technical information
How the test works
Targeted genotyping
The assay uses validated genotyping methodology to identify clinically significant DPYD variants at the positions most strongly associated with impaired fluoropyrimidine metabolism. Variant selection and interpretation follow CPIC and DPWG guidelines.
CPIC and DPWG aligned
Gene activity scores and phenotype assignments are calculated in accordance with the Clinical Pharmacogenomics Implementation Consortium (CPIC) and Dutch Pharmacogenomics Working Group (DPWG) frameworks – the two internationally recognised standards for DPYD clinical interpretation.
South African laboratory processing
All testing is performed in our South African laboratory. Results are reviewed by our genetics team before issue to the referring clinician.
References
Amstutz U, Henricks LM, Offer SM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clinical Pharmacology and Therapeutics. 2018;103(2):210-216.
Henricks LM, Lunenburg CATC, de Man FM, et al. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncology. 2018;19(11):1459-1467.
Screen before you treat.
DPYD testing takes days. Fluoropyrimidine toxicity in a poor metaboliser can be irreversible.
Results reported directly to the referring clinician, processed in South Africa.