Understanding the Importance of DPYD Pharmacogenetic Testing for Chemotherapies: A Lifesaving Measure

In the realm of personalized medicine, pharmacogenomics (PGx) plays a crucial role by tailoring medication management based on an individual’s genetic profile. This approach is designed to maximize efficacy and minimize adverse drug reactions (ADRs). One of the significant areas where PGx has made substantial advancements is in the testing for Dihydropyrimidine Dehydrogenase (DPD) deficiency, associated with the DPYD gene. Here, we explore the goals and recommendations of the Association for Molecular Pathology (AMP) Clinical Practice Committee’s Pharmacogenomics Working Group for standardizing clinical DPYD PGx testing.

The Role of DPYD in Drug Metabolism

Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, essential for metabolizing certain chemotherapeutic drugs such as 5-fluorouracil (5-FU), capecitabine, and tegafur. This enzyme is responsible for breaking down these drugs into inactive metabolites, preventing their accumulation in the body. However, individuals with a deficiency in DPD enzyme activity are at a heightened risk of severe toxicity when treated with these medications.

The Impact of DPD Deficiency

DPD deficiency is a rare autosomal recessive disorder characterized by the body's inability to metabolize and clear fluoropyrimidines efficiently. This deficiency can lead to severe and potentially life-threatening toxicities, including bone marrow suppression, gastrointestinal toxicity, and neurotoxicity. Alarmingly, partial DPD deficiency, which affects approximately 3-8% of the population, can also result in significant toxicity, making pharmacogenetic testing critical for those undergoing treatment with drugs like capecitabine or fluorouracil.

Standardizing DPYD Pharmacogenetic Testing

To address the variability in clinical PGx tests, the AMP Pharmacogenomics Working Group has set forth recommendations to standardize the key attributes of pharmacogenetic alleles for DPYD. The group has defined a minimum set of variant alleles (Tier 1) and an extended list of variant alleles (Tier 2) that clinical laboratories should include in their assays. The criteria for these tiers are based on the functional impact of the alleles, their frequency in multiethnic populations, availability of reference materials, and technical feasibility for clinical testing.

Recommendations and Guidelines

The Working Group's guidelines emphasize the importance of including clinically relevant variant alleles in PGx assays to ensure comprehensive testing. This standardization aims to reduce discrepancies in genotype interpretation, which can lead to inconsistent clinical management. By following these recommendations, clinical laboratories can enhance the reliability and clinical utility of DPYD PGx testing, ultimately improving patient safety and treatment outcomes.

Importance of Pharmacogenetic Testing

Pharmacogenetic testing can detect DPD deficiency, enabling healthcare providers to personalize treatment plans and avoid potentially fatal toxicities. For patients prescribed drugs like capecitabine or fluorouracil, this testing is a lifesaving measure. The Rxight pharmacogenetic test offered by MD Labs is designed to identify patients at risk, ensuring that they receive the safest and most effective treatment.

If you or a loved one are undergoing treatment with fluoropyrimidine-based drugs, inquire with your physician about how the Rxight pharmacogenetic test can help. This simple test using cells from a cheek swab may provide crucial information to safely guide your treatment.  At MD Labs, we are committed to advancing personalized medicine and supporting healthcare providers with the most accurate and reliable testing solutions available.

Source:
Pratt, V. M., Cavallari, L. H., Fulmer, M. L., van Schaik, R. H. N., Whirl-Carrillo, M., Weck, K. E., & all authors. (2024, July 17). DPYD Genotyping Recommendations: A Joint Consensus Recommendation of the Association for Molecular Pathology, American College of Medical Genetics and Genomics, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, Pharmacogenomics Knowledgebase, and Pharmacogene Variation Consortium. Journal of Molecular Diagnostics. https://doi.org/10.1016/j.jmoldx.2024.05.015