Understanding Your DPYD Test Result

DPYD is a gene that carries the instructions for making an enzyme called dihydropyrimidine dehydrogenase, usually shortened to DPD. This enzyme is the primary way your body breaks down a class of chemotherapy medications called fluoropyrimidines, including 5-fluorouracil (5-FU) and capecitabine (Xeloda). The DPYD test looks at this gene to predict how well your body can clear these drugs. People who inherit certain changes in DPYD make less working DPD enzyme, which means fluoropyrimidines can build up to harmful levels. Testing before treatment helps your care team choose a safe dose, or a different medication, to lower the risk of serious side effects. Because of this risk, testing before starting a fluoropyrimidine is now recommended by the United States Food and Drug Administration (FDA) and by major cancer treatment guidelines.

This article explains what the test measures, what each possible result means, and how those results are used to guide your care. A result from this test is not a diagnosis of any disease. It is information about how your body is likely to respond to a specific group of chemotherapy medications.

This test does not report a number or a reference range in the usual sense. It reports a category that describes how well your body can break down fluoropyrimidine chemotherapy, such as “normal metabolizer,” “intermediate metabolizer,” or “poor metabolizer,” often along with an activity score. Because the result reflects genes you were born with, it does not change over time and usually only needs to be tested once. What a given result means for your dose or drug choice depends on the specific medication and your treatment plan, and those decisions are made by the oncology team that prescribes your chemotherapy. Always discuss your result with your care team.

What does DPYD do?

DPYD is the gene that provides the instructions for making the DPD enzyme. An enzyme is a protein that carries out a specific chemical job in the body. The job of DPD is to break down fluoropyrimidine chemotherapy drugs, mainly 5-fluorouracil (5-FU) and capecitabine (which the body converts into 5-FU). DPD is responsible for clearing roughly 80 percent of the fluoropyrimidine that a person receives, which makes it the body’s main safety valve for these drugs.

Fluoropyrimidines work by damaging the DNA of fast-dividing cells, which is how they kill cancer cells. The DPD enzyme keeps the amount of active drug within a safe range by breaking down most of it. People who inherit certain changes, called variants, in the DPYD gene make less working DPD enzyme, or none at all. This is called DPD deficiency. With less enzyme to break the drug down, fluoropyrimidines build up and damage healthy fast-dividing cells as well as cancer cells.

The side effects of this buildup can be severe. They include mouth sores (mucositis), severe diarrhea, hand-foot syndrome (redness, swelling, and peeling of the palms and soles), and myelosuppression, which means the bone marrow slows its production of blood cells. Because the bone marrow produces red blood cells, white blood cells, and platelets, myelosuppression can lead to a low white blood cell count (increasing the risk of infection), a low platelet count (increasing the risk of bleeding), and a low red blood cell count (anemia). In people with severe or complete DPD deficiency, these reactions can be life-threatening, and in rare cases fatal, when a standard dose is given. Testing DPYD before treatment identifies people at higher risk so the dose can be adjusted or a different drug chosen in advance.

Which medications and conditions does this test apply to?

The DPYD test applies to the fluoropyrimidine chemotherapy drugs: 5-fluorouracil (5-FU), which is given by infusion, and capecitabine (Xeloda), which is taken by mouth and converted into 5-FU inside the body. A related drug, tegafur, is used in some countries and is also a fluoropyrimidine.

These drugs are among the most widely used chemotherapy medications and are part of treatment for many cancers, including colorectal cancer, breast cancer, stomach and esophageal cancer, pancreatic cancer, and head and neck cancer. Because DPD deficiency affects how a person handles the drug rather than the cancer itself, the DPYD result is useful no matter which of these cancers is being treated. Unlike some genetic tests that are ordered only for cancer, nearly everyone who has a DPYD test is a cancer patient, because these medications are chemotherapy.

How is the test performed?

The DPYD test is usually performed on a small blood sample, although some laboratories can also use a cheek swab. The sample is sent to a laboratory, where the DNA is analyzed to look for known variants in the DPYD gene. Because the gene is inherited and does not change during your life, the test generally only needs to be done once, and the result stays valid for any future fluoropyrimidine prescription.

It is important to know that laboratories test for a set of well-established DPYD variants, not every possible change in the gene. This means a “normal metabolizer” result lowers the chance of a serious reaction but does not remove it completely, because a rare variant that the test does not check for could still be present. For this reason, blood counts and side effects are still monitored closely after fluoropyrimidine treatment begins, even when the result is normal. Some centers also offer a different kind of test that measures DPD enzyme activity or a related substance in the blood (for example, a uracil blood test) rather than looking at the gene. Your care team can explain which approach was used in your case. The DPYD gene is also described in our pathology dictionary entry for DPYD.

What do the results mean?

The DPYD test sorts you into one of three categories, called a metabolizer status or phenotype, based on the variants found. Many reports also include an activity score, a number that estimates how much working DPD enzyme you have. The activity score ranges from 0 (no working enzyme) to 2 (full enzyme activity) and is the basis for the categories below. Your report may show the category, the activity score, and sometimes the name of the specific variant found (for example, DPYD*2A). The categories describe how likely fluoropyrimidine drugs are to build up to harmful levels.

Normal metabolizer (activity score 2) — Both copies of the DPYD gene work normally, so the DPD enzyme is fully active. Fluoropyrimidine drugs are expected to be processed as usual, and no dose change is needed because of DPYD. This is the most common result.
Intermediate metabolizer (activity score 1 to 1.5) — One copy of the gene carries a variant that reduces or abolishes enzyme activity, while the other functions normally. Enzyme activity is reduced, the drug builds up more than usual, and the risk of severe side effects is higher. For this result, a reduced starting dose, often around half the usual dose, is commonly considered, with the dose adjusted upward in later cycles if the treatment is well tolerated.
Poor metabolizer (activity score 0 to 0.5) — Both copies of the gene carry variants that reduce or abolish enzyme activity, so there is little or no functional enzyme. The risk of severe, and potentially life-threatening, side effects is high. When some enzyme activity remains (a score of 0.5), a fluoropyrimidine may still be used at a greatly reduced dose with very close monitoring. When there is no enzyme activity at all (a score of 0, called complete DPD deficiency), these drugs are usually avoided altogether, and a different chemotherapy is considered.

Some reports use the terms “possible poor metabolizer” or “possible intermediate metabolizer”. This is used when one of the variants found has an uncertain effect on enzyme activity. In practice, these results are usually managed cautiously, in the same way as the confirmed category to which they are closest.

Whatever the result, the DPYD test guides the decision but does not set a fixed dose on its own. Your oncology team combines the result with the specific drug, your cancer, your other treatments, and your overall health when choosing a dose or an alternative.

Why your ancestry can affect these results

Variants in the DPYD gene are found in people of all backgrounds, but the specific variants and their frequencies differ between populations. The variants most commonly included on DPYD test panels were first identified in people of European ancestry and are most common in that group. Three of these four common variants are also found in people of South Asian, East Asian, and Middle Eastern ancestry. However, some variants that reduce DPD activity are more common in other populations and are not included on every panel. For example, one variant (known as c.557A>G) is more common in people of African ancestry and is not part of some standard panels.

This matters for the amount of reassurance a normal result provides. If a panel does not include a variant that is relevant to your ancestry, a “normal metabolizer” result could miss a change that is present. It is reasonable to ask your care team which variants your test checked for, especially if you are of African, South Asian, or other non-European ancestry. This is also part of why close monitoring continues after treatment starts, regardless of the result. DPYD testing is offered to everyone starting a fluoropyrimidine, rather than limited by ancestry, because ancestry is often mixed or uncertain and any of these variants can be important.

What happens after the test?

The result of the DPYD test is used to guide your fluoropyrimidine dose or, in some cases, the choice of a different chemotherapy. A normal result supports starting at a standard dose. An intermediate result often leads to a reduced starting dose, and a poor metabolizer result may lead to a much lower dose with close monitoring or to an alternative drug, based on the specific medication and your treatment plan. Because some patients have this test after treatment has already been planned, your team will also weigh the value of waiting for the result against any need to begin treatment promptly. In urgent situations, treatment may start before the result is available, with extra caution.

Whatever the dose, your care team monitors you closely, especially during the first cycles of treatment, when severe reactions are most likely to appear. Monitoring includes checking your blood counts with a complete blood count (CBC) and watching for side effects such as mouth sores, diarrhea, and hand-foot syndrome, so that the dose can be adjusted quickly if needed.

Because these results reflect inherited genes, they can also be relevant to your biological relatives, who may carry the same variant. Family members who may need a fluoropyrimidine in the future can mention your result to their own doctors and ask whether testing is right for them. It is a good idea to keep a record of your DPYD result and to share it with any doctor who may prescribe these medications later, since the result does not change over time.

Questions to ask your doctor

What was my DPYD result, and what category did it fall into?
Was an activity score reported, and what does my score mean for my treatment?
Which specific DPYD variants does this test check for, and could a variant relevant to my ancestry have been missed?
Based on my result, will my chemotherapy dose be reduced, or should a different medication be considered?
How will I be monitored, especially during the first few cycles of treatment?
What side effects should I watch for and report right away?
If waiting for my result would delay treatment, what are the risks and benefits of starting now?
Does my result mean my biological relatives should consider testing before any fluoropyrimidine treatment?
How should I keep a record of this result for future prescriptions?
Who should I contact if I have severe side effects after my first treatment?