Chemotherapy

Fluoropyrimidines

Fluorouracil and capecitabine, the backbone of colorectal cancer treatment. One enzyme clears most of the dose, and the small number of people who lack it can be harmed severely by an ordinary dose.

What this drug connects to

The genes involved

DPYD

Colorectal Cancer →

The clearest argument on this site for testing before a first dose rather than after a bad reaction. Fluorouracil and capecitabine are the backbone of colorectal cancer chemotherapy, and one enzyme — dihydropyrimidine dehydrogenase — clears most of what is given. People carrying no-function DPYD alleles clear very little, and standard doses have caused severe and fatal toxicity. CPIC publishes dose recommendations by genotype, and pre-treatment DPYD testing is now recommended before fluoropyrimidine treatment in several health systems. Nothing here is a reason to refuse chemotherapy; it is a reason for the test to happen before it starts.

CPIC Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update, Clinical Pharmacology & Therapeutics (PMID 29152729)

In the news

2026-07-09 · CPIC (ClinPGx blog)

CPIC Comment on Pending DPYD Guideline Update

CPIC previewed a coming change to its DPYD/fluoropyrimidine guideline (the finalized version is still expected later in 2026, not yet published): the HapB3 variant this page already profiles (rs75017182, c.1129-5923C>G) will be assigned a formal activity value of 0.75 -- for a heterozygous carrier, an activity score of 1.75, with CPIC recommending starting fluoropyrimidine chemotherapy at 75% of the intended dose in the first cycle rather than full dose, then escalating based on tolerability. This is CPIC's own announced plan, not yet the finalized guideline -- flagged here as pending, not settled.

Whose work this rests on

Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update

Amstutz U, Henricks LM, Offer SM, Barbarino J, Schellens JHM, Swen JJ, Klein TE, McLeod HL, Caudle KE, Diasio RB, Schwab M

Clinical pharmacology and therapeutics · 2018 · PMID 29152729

Variants MyGeneLog™ reports for these genes

These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.

Body mass index

DPYD · rs4379706

Feeling nervous

DPYD · rs6703588

Educational attainment (MTAG)

DPYD · rs10875121

Self-reported math ability

DPYD · rs76586805

Sleep duration

DPYD · rs75641275

Sleep duration (short sleep)

DPYD · rs12567114

Substance use disorder

DPYD · rs79313673

Substance use disorder

DPYD · rs4950035

Substance use disorder

DPYD · rs11165875

Smoking initiation

DPYD · rs28552810

Educational attainment

DPYD · rs17378539

DPYD *2A — fluoropyrimidine tolerance

DPYD · rs3918290

DPYD c.2846A>T — fluoropyrimidine tolerance

DPYD · rs67376798

DPYD HapB3 — fluoropyrimidine tolerance

DPYD · rs75017182

Educational attainment

DPYD · rs7531138

Uracil levels

DPYD · rs1254152519

Smoking initiation

DPYD · rs78542688

Metabolite levels (uracil; Uracil)

DPYD · rs3790389

Smoking initiation

DPYD · rs12140043

Sodium (mean, inv-norm transformed)

DPYD · rs11165897

sodium (maximum, inv-norm transformed)

DPYD · rs2811198

Chronotype

DPYD · rs1760217

Gastroesophageal reflux disease, peptic ulcer disease and/or corresponding medications and treatment

DPYD · rs61787782

Height

DPYD · rs7519652

Highest math class taken (MTAG)

DPYD · rs12047563

Educational attainment

DPYD · rs28714464

Autism spectrum disorder or schizophrenia

DPYD · rs61789073

Educational attainment

DPYD · rs80216782

Chronic obstructive pulmonary disease

DPYD · rs114904431

Questions about Fluoropyrimidines

What are fluoropyrimidines?

Fluoropyrimidines — fluorouracil and capecitabine — are the backbone of colorectal cancer chemotherapy. One enzyme clears most of the dose, and the small number of people who lack it can be harmed severely by an ordinary dose.

Does a no-function DPYD variant mean I can’t have fluorouracil or capecitabine?

It means the standard dose isn’t safe to start with. Dihydropyrimidine dehydrogenase (DPYD) clears most of the dose of these drugs, and people carrying no-function DPYD alleles clear very little of it — standard doses in that situation have caused severe and fatal toxicity.

Is DPYD testing done before or after fluoropyrimidine chemotherapy starts?

Before. Pre-treatment DPYD testing is now recommended before fluoropyrimidine treatment in several health systems, so the dose can be set correctly from the first cycle rather than discovered to be wrong afterward.

Quoting this page

Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.

Fluoropyrimidines. MyGeneLog™. https://www.mygenelog.com/drugs/fluoropyrimidines

This page is educational and contains no dosing information. Where a clinical guideline covers one of these gene-drug pairs it is written for prescribers and works through validated algorithms alongside clinical monitoring. Nothing here is a reason to start, stop, or change a medication — that conversation belongs with the clinician or pharmacist managing your treatment.