Clinical area · Oncology

For some patients, the standard dose is an overdose.

5-fluorouracil and capecitabine are broken down by the DPD enzyme. If the enzyme is weak, the drug accumulates and reaches toxic levels even at the same dose. Testing first changes the starting dose.

Prepared by the BIODECODE science team · Last updated: October 2026 · Based on CPIC, DPWG, FDA and peer-reviewed publications

In brief

  • 5-fluorouracil and capecitabine are among the most widely used chemotherapy drugs in colorectal, breast, gastric and head and neck cancers. The body breaks down most of them with the DPD enzyme.
  • In people whose DPD enzyme is genetically weak, the drug accumulates. The standard dose can cause severe, even fatal, toxicity in these patients.
  • Pre-treatment DPYD testing allows these patients to be treated safely with a lower starting dose. The European Medicines Agency recommended testing for DPD deficiency before treatment in 2020.

Key concepts

Fluoropyrimidine

The chemotherapy class that includes 5-fluorouracil (5-FU) and its oral precursor capecitabine.

DPD enzyme

The main enzyme that breaks down fluoropyrimidines and clears them from the body. Its instructions come from the DPYD gene.

Toxicity

A harmful effect of the drug. With fluoropyrimidines it can appear as severe diarrhoea, mouth sores, falling blood counts and hand-foot syndrome.

Activity score

A score calculated from the DPYD genotype that shows how well the enzyme works. 2 means normal, 1–1.5 reduced and 0–0.5 markedly reduced activity.

How does toxicity develop?

  1. The standard dose is given

    The dose is calculated from body surface area; genetic differences are not part of the calculation.

  2. DPD cannot break the drug down

    In a patient with weak DPD, clearance slows and blood levels rise above what is expected.

  3. The drug harms healthy tissue

    The accumulated drug also hits fast-dividing healthy cells: the gut, mouth, skin and bone marrow.

What does a DPYD result mean?

Activity scoreEnzyme statusGeneral guideline recommendation*
2Normal DPD activityStandard starting dose.
1–1.5Reduced DPD activityThe starting dose is reduced and adjusted to the patient's tolerance.
0–0.5Markedly reduced or absent activityFluoropyrimidines are generally avoided; if unavoidable, a very low dose with close monitoring.

* CPIC DPYD guideline. The dose decision belongs to the oncologist, based on the treatment protocol and the patient's condition.

Who is it relevant for?

  • All patients about to start treatment containing 5-fluorouracil or capecitabine
  • Patients who had unexpectedly severe side effects after a previous cycle
  • Patients about to start a thiopurine (mercaptopurine, azathioprine) for leukaemia or autoimmune disease
  • Patients for whom irinotecan or tamoxifen is planned

Your physician decides whether the test is right for you.

Evidence

  • 30%

    Reported rate of severe toxicity with fluoropyrimidine therapy

    Henricks et al., Lancet Oncology 2018
  • 1,103

    Patients in 17 Dutch hospitals who received DPYD genotype-guided dosing

    Henricks et al., Lancet Oncology 2018
  • 2.87 → 1.31

    Severe toxicity risk in DPYD*2A carriers after genotype-guided dosing

    Same study
  • 4.30 → 0

    Reported severe toxicity in c.1679T>G carriers with a 50% dose reduction

    Same study

Related genes and drugs

GeneRoleRelated drugsSource
DPYDGene for the DPD enzyme that breaks down fluoropyrimidinesFluorouracil, capecitabineCPIC
TPMT · NUDT15Enzymes that process the toxic products of thiopurine drugsAzathioprine, mercaptopurine, thioguanineCPIC
UGT1A1Enzyme that clears irinotecan's active productIrinotecanDPWG / FDA
CYP2D6Enzyme that converts tamoxifen to its active formTamoxifenCPIC
G6PDEnzyme that protects red blood cells from oxidative damageRasburicaseCPIC

What you will see in the BIODECODE report

  • 4 key variants

    DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A are assessed directly.

  • Activity score

    DPYD activity score and phenotype, with a starting-dose recommendation from CPIC tables.

  • Gaps are stated

    For any locus without a result, the measured depth and reason are written in the report.

  • Oncology section

    Fluoropyrimidines, thiopurines and irinotecan on separate drug cards.

Sample report (PDF)

Good to know

  • The four key DPYD variants do not explain all DPD deficiency. Genotype therefore does not replace clinical monitoring.
  • Some centres use genotyping together with phenotype tests, such as measuring uracil levels in blood.
  • The test must be done before treatment begins; plan the turnaround time together with the treatment schedule.

Frequently asked questions

Does DPYD testing prevent all toxicity?

No. Not all variation in DPD activity is explained by these variants, so genotype complements clinical monitoring rather than replacing it.

Does testing delay chemotherapy?

Testing should be done before treatment starts. Plan the turnaround time with our laboratory partner and your physician.

My result was normal. Will I have no side effects?

A normal result lowers the risk of DPYD-related severe toxicity, but it does not remove the known side effects of chemotherapy. Routine monitoring continues.

References

  1. Henricks LM et al. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol. 2018.
  2. Amstutz U et al. CPIC guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018.
  3. European Medicines Agency (EMA). Recommendation on testing for DPD deficiency before treatment with fluorouracil and related medicines. 2020.
  4. Relling MV et al. CPIC guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther. 2019.
  5. Goetz MP et al. CPIC guideline for CYP2D6 and tamoxifen therapy. Clin Pharmacol Ther. 2018.

This page is for information only; diagnosis and treatment decisions belong to your physician. Never stop or change a medicine on your own.

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