DPYD testing is a genetic screening tool used before administering specific chemotherapy drugs. Its purpose is to identify individuals who may have a heightened risk of experiencing severe side effects from these treatments. This preventative measure allows medical teams to anticipate and mitigate potential adverse reactions.
The Role of the DPYD Gene in Chemotherapy
The DPYD gene holds the instructions for producing an enzyme known as dihydropyrimidine dehydrogenase (DPD). This liver enzyme’s main function is to break down a class of chemotherapy drugs called fluoropyrimidines. These drugs are commonly used to treat several types of cancer.
The two most frequently used fluoropyrimidines are 5-fluorouracil (5-FU) and capecitabine. The DPD enzyme is responsible for converting more than 85% of a clinically administered 5-FU dose into an inactive metabolite, which the body can then safely eliminate. This process prevents the drug from building up to harmful levels within the bloodstream.
Some individuals have variations within their DPYD gene that can lead to a condition called DPD deficiency, where the body produces a less effective enzyme or lower amounts of it. When a person with DPD deficiency receives a standard dose of a fluoropyrimidine, their body cannot break down the drug efficiently. This leads to a toxic accumulation of the chemotherapy agent, which can cause severe and sometimes life-threatening side effects, including intense diarrhea, painful mouth sores (mucositis), and a dangerous drop in white blood cells (neutropenia).
The DPYD Testing Process
Any patient scheduled to receive treatment with fluoropyrimidine-based drugs like 5-FU or capecitabine is a candidate for DPYD testing. The test is a preventative step to ensure the prescribed treatment plan is appropriate for the individual’s genetic makeup.
The process of getting tested is straightforward. It involves collecting a blood sample from the patient before their cancer treatment begins. In some cases, a saliva sample may be used instead. This sample is then sent to a specialized genetic laboratory for analysis.
At the lab, scientists examine the patient’s DPYD gene for specific, well-documented variations. The test screens for the most common variants known to cause DPD deficiency in certain populations, allowing oncologists to identify at-risk patients before the first dose of chemotherapy is administered.
Interpreting Test Results
The results of a DPYD gene test categorize an individual’s ability to metabolize fluoropyrimidine drugs. The findings are grouped into a few distinct classifications based on the genetic variants detected.
A “normal metabolizer” result indicates that no significant variations were found in either of the two copies of the patient’s DPYD gene. This means the DPD enzyme is expected to function correctly, and the body should be able to break down the chemotherapy drugs as anticipated.
An “intermediate metabolizer” status is assigned when a person has one altered copy of the DPYD gene and one normal copy. This genetic makeup leads to reduced DPD enzyme activity, impairing the body’s ability to process fluoropyrimidines at a normal rate.
A “poor metabolizer” has the most severe form of DPD deficiency. This result means the patient has two altered copies of the DPYD gene or specific variants that lead to a complete loss of enzyme activity. Consequently, their body has little to no ability to produce a functional DPD enzyme and cannot safely break down fluoropyrimidine drugs.
Impact on Cancer Treatment Plans
The results from DPYD testing directly influence how an oncologist will proceed with a patient’s chemotherapy. For individuals identified as normal metabolizers, the standard dosage of 5-FU or capecitabine is administered. No initial dose adjustment based on genetics is usually required.
For patients classified as intermediate metabolizers, a modification to the treatment plan is common. Oncologists will often recommend a reduced starting dose of the chemotherapy drug. Studies support a dose reduction of around 50% for these patients to lower the risk of severe toxicity. The medical team will then monitor the patient closely, and if the first cycle is well-tolerated, the dose may be cautiously increased in subsequent treatments.
When a patient is found to be a poor metabolizer, the standard approach is to avoid fluoropyrimidine drugs entirely. Administering these chemotherapies would pose a high risk of life-threatening toxic reactions. Instead, the oncologist will select an alternative chemotherapy regimen that does not rely on the DPD enzyme for breakdown, ensuring patient safety while providing an effective cancer treatment.