The NHS in England has recently commissioned testing for the DPYD gene in patients who are being considered for treatment with fluorouracil based therapies and following the recommendation on that on the 22nd October 2020 by the MRHA.

Genetics Referral Form DPYD

Below are details on how this testing is to be provided in the North East and Yorkshire by our Genomics Laboratory Hub.

Dihydropyrimidine dehydrogenase (encoded by the DPYD gene) is a protein that inactivates 80-90% of fluorouracil into 5,6-dihydro-fluorouracil, its major metabolite. Polymorphisms in DPYD are the most recognised cause of primary deficiency of DPD and can be associated with severe toxicity from chemotherapy with 5- fluorouracil or its pro-drugs capecitabine and tegafur.

DYPD testing was recommended on the 22nd October 2020 by the MRHA for all patients starting fluorouracil based therapies.

Patients planned to start a systemic treatment with fluorouracil, capecitabine or tegafur within it.

Patients who have previously been treated with a fluorouracil or pro-drug regimen without excess toxicity do not need to be tested.

The GLH (Genomics Laboratory Hub) will offer testing on a blood sample for the most common variants in DPYD that lead to DPD deficiency. i.e;

  • c. 1905+ 1G>A (rs3918290) DPYD*2A
  • c. 2846A>T (rs67376798)
  • c.1679T>G (rs55886062) DYPD*13
  • c.1236G>A/HapB3DPYD (rs56038477)

This may not detect all patients with DPYD deficiency, and patients should be informed of this at time of consent.

Estimated turnaround time will be under 7 days.

The GLH began testing on the 30th November 2020.

A 2.5ml EDTA tube (purple topped tube as used for a full blood count) should be sent to the local genetics lab using the request form. It is important that the box asking for the patient’s cancer type is appropriately ticked. If this information is not given it may delay testing.

The referring clinician and referring hospital details must also be completed clearly (without use of abbreviations) to ensure the result is reported correctly.

This is a genetic test to help predict patients who may have excess toxicity if given full doses of chemotherapy, and allow planned dose reductions.

The chance of having a DPYD variant is between 1 in 10 and 1 in 20; in most patients it will just require an adjustment in dose rather than a change in treatment.

It has no implications for their health apart from allowing appropriate dosing of this chemotherapy.

It does not need to be reported to their health insurance.

As with other genetic tests undertaken by the GLH, the result will be returned to the referring clinician by either email or uploaded to the electronic patient record as agreed by each referring Trust.

For DPYD testing, the result will also be copied to a central email address at the referring hospital if the hospital has requested this to be set up, which will usually be the pharmacy cancer team.

The result should be uploaded onto the patient’s electronic patient record or filed in their medical notes as appropriate.

Clinical teams will need to have robust systems in place to ensure results are actioned before the patient receives their first dose.  E.g. by pharmacy departments acting as gatekeepers to only supply the medicine after the result has been seen and actioned.  Further guidance on this is provided in the UK Chemotherapy Board document linked below.

UK Chemotherapy Board PDF

Guidelines as to suggested dose adjustments for patients with one DPYD variant (ie heterozygous genotype) are to be found in the UK chemotherapy guidelines which can be accessed at, or can be discussed with your cancer pharmacist.

Patients with two DPYD variant gene copies (ie homozygous or compound heterozygous genotypes) should be considered for alternative treatments.