DPYD Gene Guide for Cancer Medicines

Dihydropyrimidine dehydrogenase (DPD) is an enzyme in your body that breaks down certain medicines, called fluoropyrimidines. These medicines include 5-FU and capecitabine. A small number of people have decreased DPD enzyme activity and are call intermediate metabolizers. About 6 in 100 people are DPD intermediate metabolizers. In rare instances, individuals can have complete loss of DPD enzyme activity and are called poor metabolizers. About 2 in 1,000 people are DPD poor metabolizers.

Your medical team can make changes to your treatment if DPYD genetic testing shows you are at increased risk of experiencing severe side effects with fluoropyrimidines. A person with DPD deficiency cannot break down fluoropyrimidines normally which can result in a buildup of drugs in the body. Severe, and sometimes life-threatening side effects can happen early on during treatment in a person with DPD intermediate or poor metabolism. Some of these serious side effects include low blood counts called neutropenia, diarrhea, and blistering of the mouth, hands, or feet. In most instances, a reduction in fluoropyrimidine dose can help prevent severe toxicities for those with DPD deficiency.

DPD deficiency can be caused by variants, also called mutations, in the DPYD gene. The DPYD gene provides instructions for making the DPD enzyme. DPYD gene testing can help determine if you have a mutation that causes DPD deficiency. A blood sample will be collected and sent to the laboratory for testing. Results are usually available in one or two weeks.

Your medical team can use this information to make changes to your treatment regimen to reduce your risk of serious side effects. If you are a DPD intermediate metabolizer, your medical team may use a lower dose of 5FU or capecitabine. If you are a DPD poor metabolizer, your medical team may use very low doses of 5FU or capecitabine. In certain instances, your medical team may prefer to avoid fluoropyrimidines.  Notify your healthcare provider if genetic testing shows you have DPD deficiency, especially if you are getting care outside of Moffitt.

Your medical team may prescribe their planned dose of 5-FU or capecitabine if testing shows that you have normal DPD enzyme activity. Keep in mind that even when no DPYD gene mutation is found, some people may still develop serious side effects.  Other factors, such as drug-drug interactions, can also play a role in how the body responds to medicines. A limitation to DPYD testing is that you might have a mutation that the laboratory does not test for or a rare mutation that we do not know about yet.