DPD Deficiency and Colorectal Cancer Treatment
What is DPD deficiency and why does it matter for colorectal cancer patients?
DPD is an enzyme made in the body, and DPYD is the gene that encodes it. The DPD enzyme is required to break down 5-fluorouracil and capecitabine in the body. 5-fluorouracil, also called 5-FU, and capecitabine are chemotherapy drugs used to treat colorectal cancer and other cancers.
DPD deficiency can be complete (no enzyme function) or partial (reduced enzyme function). Complete DPD deficiency is rare, occurring in about 0.5% of people. Partial deficiency is more common and occurs in 2-8% of people.
Deficiency of the DPD enzyme is not usually a problem unless people who have it are exposed to 5-fluorouracil or capecitabine. When people with DPD deficiency receive standard doses of 5-FU or capecitabine, they are at significant risk for severe and/or life-threatening toxic effects from these drugs.
If you have a DPYD mutation leading to decreased (partial deficiency) or absent (complete deficiency) DPD enzyme, 5-FU related chemotherapy drugs are not broken down properly, leading to increased levels of 5-FU in your body. Increased 5-FU levels can lead to severe and life-threatening toxic effects. This toxicity can cause treatment delays, hospitalization, and death.
Screening for DPD deficiency can be done by measuring enzyme activity or by looking for mutations in the DPYD gene. Testing is performed on a blood sample or saliva. The time it takes to get test results can vary; current turnaround times for DPD / DPYD testing average 3-10 days.
Recommendations for pre-treatment DPD / DPYD testing are different around the world. The European Medicines Agency recommends pre-screening and therapeutic dose management. The U.S. Food and Drug Administration recommends discussing pre-treatment testing with patients. The National Comprehensive Cancer Network (NCCN) guidelines for colon, rectal, anal, and small bowel cancers were updated in March 2025 to recommend consideration of DPYD genetic varianIn practice, testing varies quite a bit between institutions and individual physicians.
Advocates for Universal DPD/DPYD Testing is a member of GCCA, and their tireless work has resulted in updates in the U.S. Food and Drug Administration (FDA) labeling of capecitabine and 5-FU to point out the risk of severe toxicity in DPD deficient patients, and to suggest physicians discuss the possible benefits of pre-screening with their patients. Their advocacy recently led to a workshop on DPYD testing held by American Association for Cancer Research and the U.S. FDA and the FDA ultimately reissued a safety warning reminding oncologists to consider physician-patient discussion on the possible benefits of prescreening for DPD deficiency. “By making DPYD testing mandatory—just as it is in Europe—the U.S. would significantly reduce preventable, treatment‑related deaths,” Karen Merritt, Co-founder of Advocates for Universal DPD/DPYD Testing, said, emphasizing the imperative of pre-treatment screening in the U.S.
The Global Colon Cancer Association supports pre-treatment screening for DPD deficiency or DPYD mutations as an essential part of colorectal cancer care to reduce the risk of severe toxicity and death from 5-FU related chemotherapy.
You can learn more about DPD, DPYD, and other chemotherapy toxicity biomarkers at knowyourbiomarker.org.