The Clinical application of DPYD and UGT1A1 Pharmacogenomic (PGx) Tests

Authors: Iva Lemberiadis and Tara Smith

If you are a prescriber of 5-FU or capecitabine, it is important to test for DPYD genetic variants. Similarly, if you prescribe irinotecan, testing for UGT1A1 variants is necessary. These tests can identify patients at increased risk of toxicity, allowing for more personalised and safer treatment plans.

DPYD PGx Testing

DPYD PGx testing identifies patients with reduced dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can lead to severe toxicity when treated with fluoropyrimidines such as 5-FU and capecitabine.

Reduced DPD enzyme activity is not uncommon, affecting approximately 3-5% of the population. For individuals with complete DPYD deficiency, 5-FU and capecitabine are contraindicated as they can result in severe or even fatal toxicity.^1,2

UGT1A1 PGx Testing

UGT1A1 PGx testing identifies patients with reduced UDP-glucuronosyltransferase 1A1 enzyme activity, which can lead to an increased risk of side effects when treated with irinotecan.

The Benefits of DPYD and UGT1A1 PGx Testing

Incorporating DPYD and UGT1A1 PGx testing into your practice may offer the following benefits for patients treated with 5-FU, capecitabine or irinotecan:

• Reduce the risk of severe drug toxicity.
• Personalise dosing regimens.
• Enhance patient safety.

Recommendations for the Use of DPYD and UGT1A1 PGx Testing in Published Clinical Guidelines

The evidence supporting DPYD and UGT1A1 PGx testing is reviewed and published in clinical PGx guidelines such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG).^3,4 These guidelines are based on a review of the literature demonstrating the clinical utility of PGx testing in guiding the prescribing of these chemotherapeutic agents.

DID YOU KNOW?

Australian resources now recommend that clinicians discuss DPYD gene testing with all patients who are about to start treatment with fluoropyrimidines (5-FU and capecitabine). The decision to conduct the testing should be made collaboratively between the clinician and the patient.⁵

myDNA: Your Partner in Expedited DPYD/UGT1A1 Result Delivery

myDNA has extensive experience in supporting Australia’s leading cancer hospitals and clinics. Our primary goal is to deliver reliable clinical services, empowering the clinician to provide the highest standard of care to their patients.

Here’s what sets myDNA apart:

• Expedited Results: Our NATA accredited laboratory located in Melbourne, Australia, provides results within 3 business days of sample receipt. This rapid turnaround time allows clinicians to make informed prescribing decisions swiftly, ensuring their patients can start chemotherapy treatment as soon as possible.
• Streamlined Testing Process: myDNA offers DPYD/UGT1A1 buccal testing kits that can be used to collect the patient’s sample during their consultation with their clinician. This ensures a simple, non-invasive process for the patient and allows for quicker delivery of results.

Discover how DPYD and UGT1A1 testing can support delivering a safer and more personalised chemotherapy treatment for your patients.

Please visit our website https://www.mydna.life/dpydtesting/; https://www.mydna.life/ugt1a1-3/

References:

1. Australian Medical Handbook, Capecitabine. 2023. [ONLINE] Available at: https://amhonline.amh.net.au/chapters/immunomodulators-antineoplastics/cytotoxic-antineoplastics/antimetabolites/capecitabine[Accessed 31 August 2023]
2. Australian Medical Handbook, Fluorouracil. 2023. [ONLINE] Available at: https://amhonline.amh.net.au/chapters/immunomodulators-antineoplastics/cytotoxic-antineoplastics/antimetabolites/fluorouracil[Accessed 31 August 2023]
3. Amstutz, U., et al. (2018). “Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update.” Clin Pharmacol Ther 103(2): 210-216.
4. [ONLINE]. Available at: https://www.pharmgkb.org/chemical/PA450085/guidelineAnnotation/PA166104951[Accessed 12 September 2022]
5. eviQ. [ONLINE] Available at: https://www.eviq.org.au/clinical-resources/side-effect-and-toxicity-management/prophylaxis-and-treatment/1744-dihydropyrimidine-dehydrogenase-dpd-enzyme#clinical-implications[Accessed 31 August 2023]