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Fluorouracil (5-FU)

Raw research findings for this medication. Mostly single studies, not curated or confirmed robust.

About Fluorouracil

What it is

Fluorouracil (5-FU) is one of the most widely used chemotherapy medicines, an antimetabolite that stands in for a DNA and RNA building block and blocks thymidylate synthase, so cancer cells cannot make DNA. It is given by drip for bowel, stomach, pancreatic, breast and head and neck cancers, usually in combinations such as FOLFOX and FOLFIRI, and as a cream for skin lesions. It is sold as Adrucil, among other names.

How genes come into it

DPYD makes dihydropyrimidine dehydrogenase, the enzyme that breaks down more than 80 percent of fluorouracil. A few DPYD variants (among them *2A, rs3918290, and c.2846A>T, rs67376798) make less working enzyme; people who carry one keep far more of the drug active, with a much higher chance of severe side effects. About 3 to 8 in 100 people of European ancestry carry one. CPIC and DPWG have published guidelines on DPYD and fluorouracil, and the US and EU labels discuss it. Other genes such as TYMS have been studied, with weaker evidence.

Published guidelines

Clinical guidelines that name a gene for Fluorouracil. They sort people into groups by the gene copies they carry.

CPIC guideline: DPYD. DPYD activity score 0 to 2. Strong. 2018.

DPWG guideline: DPYD. DPYD activity score 0 to 2. 2020.

US FDA: DPYD. DPYD activity score 0 to 0.5. 2024.

US FDA: DPYD. DPYD activity score 0 to 1.5. Data that Support Therapeutic Management Recommendations.

What research found

Every published finding on gene variants and Fluorouracil. Upload your DNA file to see which of these rows apply to you.

Rated evidence (197 rated variants)

PharmGKB weighs all studies of a variant and rates how strong the evidence is, from 1A (strongest) to 4.

DPYD rs3918290: Level 1A · replicated. Toxicity: Neoplasms. 52.

DPYD rs67376798: Level 1A · replicated. Toxicity: Neoplasms. 23.

DPYD rs3918290: Level 1A · replicated. Other. 23.

DPYD rs2297595: Level 1A · replicated. Toxicity: Neoplasms. 17.

Metabolism (15 findings)

Studies of how quickly the body processes this medication.

DPYD DPYD deficiency: DPYD deficiency is associated with clearance of fluorouracil in people with Head and Neck Neoplasms.

DPYD rs17376848: Genotypes AG + GG is associated with increased concentrations of fluorouracil in people with Colorectal Neoplasms as compared to genotype AA.

DPYD rs1801159: Genotypes CC + CT is associated with increased concentrations of fluorouracil in people with Colorectal Neoplasms as compared to genotype TT.

DPYD rs1801160: Genotypes CT + TT is associated with decreased metabolism of fluorouracil in people with Neoplasms as compared to genotype CC.

Response (184 findings)

Studies of how well it worked in people carrying a variant.

rs4932551: Allele C is associated with response to cisplatin, fluorouracil and mitoxantrone in people with Carcinoma, Hepatocellular as compared to allele G.

rs5906072: Allele T is associated with response to cisplatin, fluorouracil and mitoxantrone in people with Carcinoma, Hepatocellular as compared to allele C.

rs5934731: Allele C is associated with response to cisplatin, fluorouracil and mitoxantrone in people with Carcinoma, Hepatocellular as compared to allele T.

rs6025211: Genotypes CC + TT are associated with increased response to cisplatin, fluorouracil and mitoxantrone in people with Liver Neoplasms as compared to genotype CT.

Dosing (11 findings)

Studies of how much of the drug people needed or tolerated.

DPYD DPYD poor metabolizer: DPYD poor metabolizer is associated with decreased dose of fluorouracil in people with Colorectal Neoplasms, Gastrointestinal Neoplasms and Rectal Neoplasms as compared to DPYD normal metabolizer.

DPYD rs3918290: Genotype CT is associated with dose of capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype CC.

DPYD rs56038477: Genotype CT is associated with dose of capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype CC.

DPYD rs67376798: Genotype AT is associated with dose of capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype TT.

Side effects (6 findings)

Studies of side effects in people carrying a variant.

DPYD rs3918290: Genotype CT is associated with decreased clearance of fluorouracil in people with Colorectal Neoplasms as compared to genotype CC.

DPYD rs67376798: Genotype AT is associated with decreased clearance of fluorouracil in people with Colorectal Neoplasms as compared to genotype TT.

TYMS rs183205964: Allele C is associated with increased discontinuation of capecitabine, fluorouracil or tegafur in people with Neoplasms as compared to allele G.

DPYD rs67376798: Genotype AT is associated with increased exposure to fluorouracil in women with Colonic Neoplasms.

Study findings and evidence levels: PharmGKB (CC BY-SA 4.0). Guidelines: CPIC and DPWG, as bundled in PharmCAT. Most studies were done mainly in people of European ancestry.

Related Drugs

More drugs from the same category

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Cytosar-U (Antimetabolites)

Fludara (Antimetabolites)

Not a prescribing recommendation. This page is educational information about pharmacogenomic research and clinical guidelines - it is not medical or dosing advice, and not a prediction of how any medication will work for you. Never start, stop, or change a medication or dose based on it; talk to your doctor or pharmacist, who can order clinical-grade testing if appropriate.

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Content updated September 2026.

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