The DPYD gene is a human gene that provides instructions for making an enzyme called dihydropyrimidine dehydrogenase (DPD). This enzyme plays a crucial role in breaking down (metabolizing) the chemotherapy drugs fluorouracil (5-FU) and capecitabine.
Function of the DPYD Gene and DPD Enzyme
-
Metabolizing Fluorouracil and Capecitabine: The DPD enzyme, produced by the DPYD gene, is primarily responsible for breaking down more than 80% of fluorouracil and its prodrug capecitabine. These drugs are commonly used to treat various cancers, including colorectal, breast, and gastric cancers.
-
Impact of DPYD Gene Variations: Genetic variations (mutations) in the DPYD gene can lead to reduced or absent DPD enzyme activity. When this happens, the body is unable to properly break down fluorouracil and capecitabine.
DPYD Deficiency and Fluorouracil Toxicity
-
Increased Risk of Toxicity: Individuals with a DPYD deficiency (due to variations in the DPYD gene) are at a significantly higher risk of experiencing severe and potentially life-threatening side effects from fluorouracil and capecitabine. These side effects can include:
- Myelosuppression (bone marrow suppression, leading to low blood cell counts)
- Mucositis (inflammation and ulceration of the mucous membranes)
- Diarrhea
- Neurotoxicity (damage to the nervous system)
- Hand-foot syndrome (pain, swelling, and redness of the hands and feet)
-
DPYD Testing: Because of the risk of toxicity, testing for DPYD gene variants is increasingly recommended, and sometimes required, before starting treatment with fluorouracil or capecitabine. This testing helps identify individuals who may need a reduced dose of the drug or alternative treatments.
-
Example Variants: Some common DPYD variants associated with reduced DPD activity include DPYD 2A, DPYD 13, DPYD c.2846A>T, and DPYD c.1679T>G. The specific variants tested can vary depending on the testing laboratory and guidelines.
Clinical Significance
Understanding the DPYD gene and its role in drug metabolism is essential for:
- Personalized Medicine: Tailoring cancer treatment based on an individual's genetic makeup to maximize efficacy and minimize toxicity.
- Improved Patient Outcomes: Reducing the incidence of severe fluorouracil-related side effects and improving the overall quality of life for cancer patients.
- Informed Decision-Making: Providing clinicians with valuable information to make informed decisions about drug dosage and treatment strategies.
In summary, the DPYD gene is critical for metabolizing fluorouracil and capecitabine, and variations in this gene can lead to DPD deficiency and severe chemotherapy toxicity, making DPYD testing increasingly important in cancer treatment.
