A CPIC dosing guideline for two widely used chemotherapy drugs, 5-fluorouracil and capecitabine -- three DPYD alleles that reduce the enzyme that breaks the drug down, each with its own guideline-recommended dose cut.
5-fluorouracil (5-FU) and capecitabine, its oral prodrug form, are fluoropyrimidine chemotherapy drugs used widely across colorectal, breast, and other solid-tumor cancers. Dihydropyrimidine dehydrogenase (DPYD) is the enzyme responsible for breaking these drugs down; someone with reduced DPYD activity clears the drug more slowly, exposing their body to a standard dose for longer -- and fluoropyrimidine toxicity at a standard dose in a DPYD-deficient person can be severe, in some cases fatal.
The guideline behind this page catalogues three DPYD variant alleles, each independently reducing enzyme activity to a different degree: rs3918290 (DPYD*2A), rs67376798 (DPYD c.2846A>T), and rs75017182 (DPYD HapB3). CPIC's guideline gives a specific starting-dose reduction recommendation for each, since they are not interchangeable -- the degree of activity loss, and so the recommended dose adjustment, differs by which allele (or combination of alleles) someone carries.
This is one of the more consequential pharmacogenomic tests in oncology specifically because the failure mode is severe and because DPYD deficiency is otherwise invisible before a first dose is given -- unlike many drug-response genes, where a poor-metaboliser genotype mainly means a drug works less well, DPYD deficiency at standard fluoropyrimidine doses is a genuine, recognized cause of severe, sometimes fatal toxicity, which is exactly why CPIC assigns this pairing its highest evidence and actionability grade.
Where DPYD genotype is known before treatment starts, CPIC's guideline is used to select a reduced starting dose rather than a standard one, with the exact reduction depending on which allele(s) are present and whether one or two copies are carried. The dose is then titrated based on how the patient tolerates it, the same as any chemotherapy regimen -- genotype informs the starting point, not the entire course. This is a decision made by the treating oncologist, not something to self-interpret from a genotype alone.
This is guideline information, not a personal dosing instruction. CPIC's guideline gives dose-reduction recommendations by genotype for an oncologist to apply before a fluoropyrimidine is first given; it does not set an individual's dose or treatment plan by itself.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Fluoropyrimidine Dosing (DPYD) comes down to these specific, well-studied positions — not a diagnosis.
Databases, guidelines and references
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Fluoropyrimidine Dosing (DPYD). MyGeneLog™. https://www.mygenelog.com/conditions/fluoropyrimidine-dosing
No. It describes what CPIC's published guideline recommends based on DPYD genotype, for an oncologist to apply -- an individual's actual treatment plan is an oncology decision, not something to determine from this page.
Fluoropyrimidines: 5-fluorouracil (5-FU) and its oral prodrug capecitabine, used across colorectal, breast and other solid-tumor cancers.
Not with certainty. These are the best-characterized DPYD alleles CPIC's guideline addresses, but rarer variants can also reduce DPYD activity, and the guideline itself does not describe this as an exhaustive test.
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