DPYD

The DPYD gene provides the instructions for making an enzyme called dihydropyrimidine dehydrogenase (DPD). This enzyme plays an important role in the body’s ability to break down and eliminate certain chemotherapy drugs, especially medications used to treat cancer such as 5-fluorouracil (5-FU) and capecitabine.

What does the DPYD gene do?

The DPD enzyme made by the DPYD gene is responsible for breaking down fluoropyrimidine drugs, which include 5-FU and capecitabine. These drugs are commonly used to treat cancers of the colon, breast, stomach, esophagus, and head and neck. The DPD enzyme also helps break down natural substances called pyrimidines, which are used to build DNA and RNA in all cells.

If the body does not make enough of the DPD enzyme, it cannot break down these chemotherapy drugs properly. As a result, the drugs can build up to dangerous levels in the body and cause severe or life-threatening side effects.

Why is DPYD testing important?

Some people inherit changes, or variants, in the DPYD gene that reduce or eliminate the activity of the DPD enzyme. These people are at much higher risk of experiencing serious side effects if they receive standard doses of 5-FU or capecitabine.

Testing for changes in the DPYD gene helps identify people who may need lower doses of chemotherapy or who should receive alternative treatments. This is an important step in making cancer treatment safer and more personalized.

How do doctors test the DPYD gene?

Testing for the DPYD gene is usually done using a blood sample or cheek swab. The sample is sent to a laboratory, where the DNA is analyzed to look for common variants that are known to reduce DPD enzyme activity.

Some laboratories may also test the enzyme activity directly, although this is less commonly done.

DPYD testing is often performed before starting chemotherapy with 5-FU or capecitabine, especially if these drugs are expected to be given at high doses or over a long period.

What do the test results mean?

A DPYD test result will show whether any variants were found in the gene and how they may affect enzyme activity:

• No variants found – DPD enzyme activity is likely normal. Standard doses of chemotherapy are usually considered safe.

• One variant found (partial deficiency) – Enzyme activity may be reduced. A lower starting dose of chemotherapy is usually recommended, with close monitoring.

• Two variants found (complete or near-complete deficiency) – Enzyme activity is very low or absent. These patients are at high risk for severe side effects. Doctors will often recommend alternative treatments that do not rely on DPD for breakdown.

What does it mean if I have a DPYD variant?

Having a variant in the DPYD gene means that your body may not break down certain chemotherapy drugs effectively. It does not mean that you have cancer or any other disease. Instead, this information is used to help guide your treatment and prevent harmful side effects.

Knowing your DPYD status allows your doctor to make safer, more personalized decisions about your care. In some cases, this information may also be helpful for close family members who could carry the same genetic changes.

What treatments are affected by DPYD status?

The drugs most affected by DPD enzyme activity are:

• 5-fluorouracil (5-FU) – often given by injection

• Capecitabine – a pill that is converted into 5-FU in the body

• Tegafur – less commonly used, but also converted into 5-FU

These drugs are used in the treatment of many common cancers, especially those involving the digestive tract, breast, and head and neck.

If your test shows reduced DPD activity, your doctor may recommend dose adjustments, close monitoring, or using a different medication altogether.

Questions to ask your doctor

• Was I tested for DPYD variants before starting chemotherapy?

• What do my DPYD results mean for my treatment?

• Are dose changes or alternative treatments recommended?

• Could this result affect other medications I take in the future?

• Should my family members consider genetic testing?