DPD Deficiency for 5-FU Response

Is Testing Right for Me? I Have My Test Results

DPD Deficiency for 5-FU Response

How Testing Works for 5-Fluorouracil Response

DPD deficiency testing for 5-FU response can be done in two different ways. Genetic testing looks directly at the DNA of your DPYD gene. Enzyme/analyte testing checks the level of DPD activity in your blood or urine. There is conflicting information about which test is better than the other. There may be certain reasons a doctor prefers or recommends one over the other. Some doctors prefer to test patients using both methods. Your doctor can explain which type of testing would be right for you

Genetic Testing

Genetic testing for 5-fluorouracil response looks for changes in the DPYD gene. This can be done in three ways.

  1. Single mutation testing. This tests looks for the most common variant, called DPYD*2A. It will tell you whether you have no, one or two copies of this variant. About 25% of people with severe toxic reactions to 5-FU have this variant. This test doesn't look for other, rare variants in the DPYD gene. So, if you test negative with this test, it's still possible to have DPD deficiency due to a different cause.
  2. Extended panel testing. These tests look for the most common variant, DPYD*2A, and some other rare variants. Some panels also look for variants in two other genes, called TYMS and MTHFR, that can cause toxic reactions to 5-FU. If you test negative with an extended panel test, it's still possible to have DPD deficiency due to a different cause.
  3. Full gene sequencing. This test looks at each "letter" of DNA in the DPYD gene to see if there are any changes. About 70% of people who develop severe side effects from 5-FU will have a variant found by gene sequencing. Because this test looks at the whole gene, it will tell you for sure if you have a DPYD variant. It's also possible, for the lab to find a variant of unknown significance. This means that the lab doesn't know if the variant causes DPD deficiency or not.

The majority of 5-FU — about 80% — is broken down by the DPD enzyme. But other enzymes are also involved in metabolizing 5-FU. Genetic testing won't tell you about other factors that affect how your body breaks down 5-FU. Some people who don't have a genetic variant still develop severe side effects from 5-FU.

Enzyme and Analyte Testing

These tests measure the amount of DPD enzyme in your blood or the amount of other biochemical products broken down by the DPD enzyme.

  1. Enzyme testing. One way to test for DPD deficiency is tomeasure the amount of DPD enzyme in a blood sample. Laboratories generally report the level and interpret it as normal, intermediate, low, or deficient. People who have lower-than-average DPD levels may still be able to take 5-FU but at a lower dose.
  2. Analyte testing. Another way to test for DPD deficiency is to measure a biochemical in the body that is broken down by the DPD enzyme, called uracil. Low levels of uracil in a person's blood or urine sample are a sign of DPD deficiency.

A key advantage of enzyme and analyte testing is that they directly measure how the DPD enzyme is working. Genes as well as non-genetic factors can cause DPD deficiency. These tests will find any lower enzyme activity, regardless of the reason.

Next: Pros and Cons

Why are you considering DPD deficiency testing for 5-FU response?

I am considering starting 5-FU to treat a medical condition.

I am currently taking/using 5-FU and I'm not having any problems with it.

I am currently taking/using 5-FU and I'm having side effects.

None of these

DPD deficiency testing for 5-FU response may be useful for you. Some people have an increased sensitivity to 5-FU and are at risk for severe side effects. People with a known DPD deficiency (not enough DPD enzyme) should not take 5-FU. People who develop symptoms of DPD deficiency while taking 5-FU should stop taking it. However, the FDA does not require or recommend testing for DPD deficiency before this drug is prescribed. At this point, the testing decision is left up to the doctor and the patient.

You should talk to your doctor to learn if DPD deficiency testing would make a difference for your healthcare. The table below sums up how test results may change your care.

Test Result Chance To Get This Result
What This Result Means
Normal DPD ~92%
  • You metabolize the drug normally.
  • You have a lower chance for side effects.
  • You can take the usual dose of the drug.
Intermediate DPD ~7%
  • You metabolize the drug more slowly.
  • You may have a higher chance for side effects.
  • Most people with this result can still take 5-FU, but should start with half the usual dose.
Low or absent DPD~1%
  • You cannot effectively metabolize this drug.
  • You have a high risk of toxic side effects.
  • You should not take this drug. Your doctor may consider a different treatment for you.

DPD deficiency testing for 5-FU response may not be useful for you. Some people have an increased sensitivity to 5-FU and are at risk for severe side effects. People with a known DPD deficiency (not enough DPD enzyme) should not take 5-FU. People who develop symptoms of DPD deficiency while taking 5-FU should stop taking it. However, the FDA does not require or recommend testing for DPD deficiency when this drug is prescribed. At this point, the testing decision is left up to the doctor and the patient.

Most people who have DPD deficiency will show signs of 5-FU toxicity after the first treatment. Since you are taking/using the drug without any side effects, testing at this point is probably not that helpful for you. You should continue to be monitored for side effects like everyone else who takes/uses 5-FU. Be sure to mention any concerns or issues you might be having with your doctor immediately.

DPD deficiency testing for 5-FU response may be useful for you. Some people have an increased sensitivity to 5-FU and are at risk for severe side effects. People with a known DPD deficiency (not enough DPD enzyme) should not take 5-FU. People who develop symptoms of DPD deficiency while taking 5-FU should stop taking it. However, the FDA does not require or recommend testing for DPD deficiency when this drug is prescribed. Some doctors may decide that testing is useful to find out if DPD deficiency explains your side effects.

  • If testing finds two gene variants and/or low-to-absent levels of DPD, you have high risk for drug toxicity. You should not take 5-FU. These results likely explain your side effects. Your doctor may want to try a different treatment.
  • If testing finds a gene variant and/or intermediate levels of DPD, you may have a higher risk for drug toxicity, but you may be able to tolerate a lowered dose. Your doctor may try lowering your dose, or your doctor may talk to you about changing to a different treatment.
  • If your test results are normal, DPD deficiency is not likely the cause of your side effects. Other factors may be affecting the way you break down this drug. Your doctor will have to make a decision about whether to lower your dose or change to a different drug therapy by weighing the benefits you are getting against the side effects.

DPD deficiency testing for 5-FU response may not be useful for you. Testing is not recommended for people who aren't starting or currently taking 5-FU. See Who Should Consider Testing for the main reasons for testing.

If you have a reason for testing that isn't covered here, talk to your doctor or a genetic counselor about whether testing might be useful for you.