DPYD is a gene that affects how your body breaks down toxic fluoropyrimidine related chemotherapy drugs (like 5-FU, 5-fluorouracil) into non-toxic forms. 5-FU related chemotherapy is used to treat colorectal cancer because its toxicity kills cancer cells. However, if you do not have enough of the enzyme that breaks down 5-FU, the levels of 5-FU can build up in your body and lead to severe toxic effects.
DPYD is the gene that encodes an enzyme called “dihydropyrimidine dehydrogenase” or DPD. That means that the DPYD gene gives your cells the instructions to make the DPD enzyme. The DPD enzyme is needed to break down (metabolize) 5-FU related chemotherapy drugs in your body. Mutations in the DPYD gene can cause DPD enzyme deficiency, that is, they can reduce the amount or activity of your DPD enzyme.
DPD deficiency can be partial (reduced DPD enzyme activity) or complete (no DPD enzyme activity). When your healthcare team talks about DPYD as it is related to cancer treatment, they are talking about partial DPD deficiency. 2-8% of the world’s population has a DPYD mutation causing decreased DPD (partial deficiency). Partial DPD deficiency usually causes no symptoms and only becomes known when a person has genetic testing or has severe toxic effects from 5-FU related chemotherapy. (Complete DPD deficiency is very rare. It occurs in less than 0.5% of people, and usually causes neurologic (brain-related) problems that are diagnosed in infancy.)
DPYD mutations are important because they affect your risk of treatment side effects. If you have a DPYD mutation causing decreased DPD enzyme, fluoropyrimidine chemotherapy drugs are not broken down properly, leading to increased levels of 5-fluorouracil (5-FU) in your body. Increased 5-FU levels can lead to severe toxicity and even life-threatening toxic effects.
Mutations in the DPYD gene are hereditary. If a family member has a DPYD mutation causing partial DPD enzyme deficiency, it will not affect their health unless they are given 5-FU related chemotherapy at some point in their lives. DPYD mutations do not cause colorectal cancer, and colorectal cancer does not cause DPYD mutations.
Testing for DPYD mutation before starting treatment with 5-fluorouracil related chemotherapy identifies about 50% of the patients who will develop severe toxicity from 5-FU. The other 50% of people who develop severe toxicity have those adverse effects for reasons not related to DPYD and the DPD enzyme.
When testing for DPYD, your medical team is looking specifically at your genes and/or enzyme levels, not your tumor’s genes and enzymes. DPYD is tested in a blood sample or in cells collected from your mouth or saliva.
DPYD can be tested by looking at the DNA sequence of the gene to look for a mutation (genotyping). It can also be tested by measuring the DPD enzyme level or activity to look for reduced amounts or reduced function (phenotyping).
Both genotyping and phenotyping are good ways to determine whether your DPYD status puts you at high risk for severe 5-FU toxicity.
For a DPYD phenotype test, your results will be reported as normal DPD enzyme activity, decreased DPD enzyme activity (partial DPD deficiency), or absent DPD enzyme activity (complete DPD deficiency).
For a DPYD genotype test, your results may be reported as “DPYD wild-type” which means you have no DPYD mutation. Or, if you do have a DPYD mutation causing DPD deficiency, your results will be reported as “DPYD mutant” and may list the specific mutation found.
If your DPYD genetic testing result is wild-type (WT) or your DPD enzyme level is normal
If your DPYD has a mutation that causes decreased DPD enzyme activity (partial DPD deficiency)
All colorectal cancer patients who experience severe toxicity from 5-fluorouracil related chemotherapy (5-FU, FOLFOX, FOLFIRI, capecitabine) should be tested for DPYD mutations or DPD enzyme deficiency.
Recommendations for pre-treatment DPYD testing are different around the world. Talk to your healthcare team about whether pre-treatment testing would benefit you.
A biomarker is a piece of information about your health. Biomarkers include your blood pressure, your blood type, and cholesterol or blood sugar levels measured in a blood test. The biomarkers of cancer are also known as tumor markers.