Drug/Small Molecule:
fluorouracil

Available Guidelines

  1. CPIC Dosing Guideline for fluorouracil and DPYD
  2. Dutch Pharmacogenetics Working Group Guideline for fluorouracil and DPYD

last updated 07/30/2014

CPIC Dosing Guideline for fluorouracil and DPYD

Summary

The CPIC Dosing Guidelines for fluoropyrimidines (i.e. 5-fluorouracil, capecitabine or tegafur) recommends an alternative drug for patients who are homozygous for DPYD non-functional variants - *2A (rs3918290), *13 (rs55886062), and rs67376798 A (on the positive chromosomal strand) - as these patients are typically DPD deficient. Consider a 50% reduction in starting dose for heterozygous patients (intermediate activity).

Annotation

May 2014 Update on PharmGKB

December 2013 Publication

Accepted article preview online August 2013; Advance online publication October 2013.

  • Guidelines regarding the use of pharmacogenomic tests in dosing for fluoropyrimidines have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
  • These guidelines are applicable to:
    • at the time of this writing, there are no data available on the possible role of DPYD*2A, *13, or rs67376798 in 5-fluorouracil toxicities in pediatric patient populations; however, there is no reason to suspect that DPYD variant alleles would affect 5-fluorouracil metabolism differently in children compared to adults.
  • Excerpt from the fluoropyrimidine dosing guideline based on DPYD genotype:
    • "The strength of the dosing recommendations is based on the fact that some variants (DPYD*2A, *13, and rs67376798) clearly affect DPD activity, and DPD activity is clearly related to 5-fluorouracil clearance, and 5-fluorouracil exposure is associated with its toxic effects. Therefore, reduction of fluoropyrimidine dosage in patients with these variants may prevent severe and possibly life-threatening toxicities. However, available evidence does not clearly indicate a degree of dose reduction needed to prevent fluoropyrimidine related toxicities...[Based on literature review (see full manuscript),] our recommendation is to start with at least a 50% reduction of the starting dose followed by an increase in dose in patients experiencing no or clinically tolerable toxicity to maintain efficacy, a decrease in dose in patients who do not tolerate the starting dose to minimize toxicities or pharmacokinetic guided dose adjustments (if available). Patients who are homozygous for DPYD*2A, *13, or rs67376798 may demonstrate complete DPD deficiency and the use of 5-fluorouracil or capecitabine is not recommended in these patients."
  • Download and read:

Table 1: Recommended dosing of fluoropyrimidines by genotype/phenotype.

Adapted from Tables 1 and 2 of the 2013 guideline manuscript.

Phenotype (genotype) Examples of diplotypes Implications for phenotypic measures Dosing recommendations Classification of recommendations a
Homozygous wild-type or normal, high DPD activity (two or more functional *1 alleles) *1/*1 Normal DPD activity and "normal" risk for fluoropyrimidine toxicity Use label-recommended dosage and administration Moderate
Heterozygous or intermediate activity (~3-5% of patients), may have partial DPD deficiency, at risk for toxicity with drug exposure (one functional allele *1, plus one nonfunctional allele - *2A, *13 or rs67376798A c) *1/*2A; *1/*13; *1/ rs67376798A c) Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs Start with at least a 50% reduction in starting dose followed by titration of dose based on toxicity b or pharmacokinetic test (if available) Moderate
Homozygous variant, DPD deficiency (~0.2% of patients), at risk for toxicity with drug exposure (2 nonfunctional alleles - *2A, *13 or rs67376798A c) *2A/*2A; *13/*13; rs67376798A c / rs67376798A c Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs Select alternate drug Strong

a Rating scheme described in 2013 supplement.
b Increase the dose in patients experiencing no or clinically tolerable toxicity to maintain efficacy; decrease the dose in patients who do not tolerate the starting dose to minimize toxicities.
c Note that the rs67376798A allele refers to the allele on the positive chromosomal strand. This is important because DPYD is on the minus chromosomal strand and rs67376798 is a T/A snp. Therefore, the T allele on the gene confers the deficiency, while the complement on the positive chromosomal strand (A allele) is indicative of deficiency.


last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for fluorouracil and DPYD

Summary

An alternative drug rather than fluorouracil is recommended for DPYD poor metabolizer patients, and a reduced dose (by 50%) of fluorouracil or use of an alternative drug is recommended for intermediate metabolizer patients.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for fluorouracil based on DPYD genotype [Article:21412232]. They recommend that an alternate drug be used for poor metabolizer patients, and a reduced dose or alternate drug for intermediate metabolizer patients.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
PM (2 inactive alleles, 2 decreased activity alleles, or one inactive and one decreased activity alleles) Select alterantive drug. Tegafur is not a suitable alternative because this drug is also metabolized by DPD. Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
IM (1 active allele and 1 inactive or decreased activity allele) Reduce dose by 50% or select alternative drug. Tegafur is not a suitable alternative because this drug is also a substrate for DPD. Increase dose in response to toxicity and efficacy. Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
Allele Type Alleles
active *1, *4, *5, *6, *9A
decreased activity *9B, *10
inactive *2A, *3, *7, *8, *11, *12, *13, 496A>G, IVS10-15T>C, 1156G>T, 1845G>T
  • *See Methods or PMID: 18253145 for definition of "moderate" quality.
  • S: statistically significant difference.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for fluorouracil and DPYD

This label is on the FDA Biomarker List
Actionable PGx

Summary

Carac (fluorouracil) should not be used in patients with dihydropyrimidine dehydrogenase (DPD or DPYD) enzyme deficiency as this can lead to cytotoxic activity and potential toxicities.

Annotation

Fluorouracil is available in both a topical cream and as an injection. These two formulations have slightly different indications. The cream, Carac, is used to treat multiple actinic or solar keratoses of the face and anterior scalp. The injection is used for the treatment of various types of neoplasms including colorectal neoplasms. This drug label is for Carac, the cream. Other drug labels for fluorouracil can be found on DailyMed. Both formulations advise that variants in the DPYD gene (also known as dihydropyrimidine dehydrogenase and DPD) are associated with increased risk for adverse events. See the Fluroropyrimidine Pathway and DPYD VIP for more information.

Excerpts from the fluorouracil (Carac) drug label:

Carac should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the enzyme dihydropyrimidine dehydrogenase (DPD). DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities.

Patients should discontinue therapy with Carac if symptoms of DPD enzyme deficiency develop.

Rarely, unexpected, systemic toxicity (e.g. stomatitis, diarrhea, neutropenia, and neurotoxicity) associated with parenteral administration of fluorouracil has been attributed to deficiency of dihydropyrimidine dehydrogenase 'DPD' activity. One case of life-threatening systemic toxicity has been reported with the topical use of 5% fluorouracil in a patient with a complete absence of DPD enzyme activity... Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Fluorouracil drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Leukemia
    • Adverse reactions section, Precautions section
    • source: PHONT
  • Mental Retardation
    • Precautions section
    • source: PHONT
  • Neoplasms
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Neutropenia
    • Warnings section, Adverse reactions section
    • source: PHONT
  • Stomach Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • DPYD
    • Contraindications section, Warnings section, toxicity
    • source: FDA Label

Pharmaceuticals and Medical Devices Agency, Japan (PMDA) Label for fluorouracil and DPYD

Actionable PGx

Summary

The PMDA package insert for fluorouracil states that severe adverse events have occurred in patients receiving the drug who are dihydropyrimidine dehydrogenase (DPD)-deficient. DPD is the enzyme responsible for the degradation of fluorouracil and other fluoropyrimidines.

Annotation

Please note that the information contained within this drug label annotation is sourced from Shimazawa and Ikeda (2013), whose paper provided a translation of the pharmacogenetic information contained in the PMDA package insert.

Excerpt from the package insert for fluorouracil:

Rarely, there are patients with a deficiency of dihydropyrimidine dehydrogenase (DPD), which is a catabolic enzyme of fluorouracil. Severe adverse events (eg, stomatitis, diarrhea, blood dyscrasias and neurotoxicity) associated with fluorouracils in initial treatment have been reported in these patients.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the fluorouracil package insert (in Japanese).

*Disclaimer: The contents of this page have not been endorsed by the PMDA and are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label

  • DPYD
    • Precautions section, toxicity
    • source: Pharmaceuticals and Medical Devices Agency, Japan (PMDA) Label

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
TheraGuide 5-FU rs34743033 , DPYD Full gene sequence analysis
Genelex Fluorouracil (5-FU) and DPD Enzyme Deficiency Variant in DPYD
ARUP 5-Fluorouracil (5-FU) Toxicity and Chemotherapeutic Response, 7 Mutations : 2007228 DPYD*13, DPYD*2A, DPYD*9A , rs1801131 , rs1801133 , rs67376798 , rs16430 , DPYD DPYD c.-1590T>C
Myriad TheraGuide 5-FU (includes DNA sequencing of all 23 coding exons and approximately 690 adjacent intronic base pairs of the DPYD gene.) DPYD*10, DPYD*11, DPYD*12, DPYD*13, DPYD*2A, DPYD*2B, DPYD*3, DPYD*4, DPYD*5, DPYD*6, DPYD*7, DPYD*8, DPYD*9A, DPYD*9B , rs67376798 , rs34743033 , rs34743033
GenPath Dihydropyrimidine Dehydrogenase (DPD) Gene Mutation Analysis (DPD-5 FU) rs3918290
EntroGen DPYD Genotyping Kit - Fluorouracil Toxicity rs3918290
Labcorp DPD 5-Fluorouracil Toxicity (511176) rs3918290
MDL Dihydropyrimidine Dehydrogenase (DPD Enzyme Deficiency) rs3918290
Quest Dihydropyrimidine Dehydrogenase (DPD) Gene Mutation Analysis rs3918290
23andMe Fluorouracil Toxicity DPYD*2A
5-FU GenoChip (PharmGenomics) DPYD*10, DPYD*12, DPYD*13, DPYD*2A, DPYD*3, DPYD*4, DPYD*7 , rs1801268 , rs67376798 , rs3918290 , rs72549303 , rs55886062 , rs1801158 , rs78060119 , rs2297595 , DPYD M166V , DPYD A551T (1651G>A) , DPYD D949V

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No VIP available No VIP available CYP2A6 *1B1 N/A N/A N/A
No VIP available No VIP available VA DPYD *1 N/A N/A N/A
No VIP available No VIP available VA DPYD *2A N/A N/A N/A
No VIP available No VIP available VA DPYD *5 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *1 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *6 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *28 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs10049380 124487443T>C, 2017+417A>G, 30982589T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs10209881 10068136T>C, 130-30376A>G, 31246249T>C, 315-57081A>G, 70-30376A>G, 903-30376A>G
T > C
Intronic
No VIP available CA VA
rs1042522 -278-661C>G, 16397C>G, 215C>G, 7182846G>C, 7579472G>C, 98C>G, P53:Arg72Pro, Pro33Arg, Pro72Arg, R72P, TP53 Arg72Pro, mRNA 412C>G, p.Pro72Arg, p52 codon 72
G > C
5' Flanking
Pro33Arg
No VIP available No Clinical Annotations available VA
rs10434 *847A>G, *913A>G, *929A>G, 20260A>G, 43693212A>G, 43753212A>G
A > G
3' UTR
No VIP available CA VA
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
No VIP available No Clinical Annotations available VA
rs1047840 1765G>A, 242042301G>A, 35560080G>A, 35809G>A, Glu589Lys
G > A
Missense
Glu589Lys
No VIP available No Clinical Annotations available VA
rs1051266 3952235T>C, 46957794T>C, 80A>G, 9592A>G, : 80A>G, His27Arg, RFC-1, SCL19A1:80G>A, SLC19A1:Arg27His, SLC19A1:G80A, mRNA 199A>G
T > C
Missense
His27Arg
No VIP available No Clinical Annotations available VA
rs1059829 *1103C>T, 12204956G>A, 151042029G>A
G > A
3' UTR
No VIP available No Clinical Annotations available VA
rs10784749 31565335C>G, 69422029C>G
C > G
Not Available
No VIP available No Clinical Annotations available VA
rs10876844 18194012C>A, 56050706C>A
C > A
Not Available
No VIP available No Clinical Annotations available VA
rs112723255 -14+175G>A, -14+420G>A, -368G>A, -398G>A, 1393G>A, 1408G>A, 22611C>T, 50964255C>T, 549478C>T, 5614G>A, 9260G>A, Ala465Thr, Ala470Thr
G > T
G > C
5' Flanking
Ala470Thr
No VIP available No Clinical Annotations available VA
rs1128503 1236T>C, 167964T>C, 25043506A>G, 87550285A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Not Available
Gly412Gly
No VIP available No Clinical Annotations available VA
rs1138272 12659374C>T, 341C>T, 67353579C>T, 7514C>T, A114V, Ala114Val, GSTP1: A114V, GSTP1: C341T
C > T
Missense
Ala114Val
No VIP available CA VA
rs11479 -14+194C>T, -14+439C>T, -349C>T, -379C>T, 1412C>T, 1427C>T, 22592G>A, 50964236G>A, 549459G>A, 5633C>T, 9279C>T, Ser471Leu, Ser476Leu
C > G
C > A
5' Flanking
Ser476Leu
No VIP available CA VA
rs115232898 226586A>G, 557A>G, 68136948T>C, 98165030T>C, Tyr186Cys, Y186C, c.557A>G
T > C
Missense
Tyr186Cys
No VIP available No Clinical Annotations available VA
rs115632870 151-69G>A, 68265739C>T, 97795G>A, 98293821C>T, IVS2-69, c.151-69G>A
C > T
Intronic
No VIP available CA VA
rs11615 18191871A>G, 354T>C, 45923653A>G, 63434T>C, Asn118=, ERCC1:19007T>C, ERCC1:Asn118Asn
A > G
Synonymous
Asn118Asn
No VIP available CA VA
rs12613732 10071314T>G, 130-33554A>C, 31249427T>G, 315-60259A>C, 70-33554A>C, 903-33554A>C
T > G
Intronic
No VIP available CA VA
rs12659 15830T>C, 3945997A>G, 46951556A>G, 576T>C, 696T>C, Pro192=, Pro232=
A > G
Synonymous
Pro192Pro
No VIP available No Clinical Annotations available VA
rs12999804 10067537A>T, 130-29777T>A, 31245650A>T, 315-56482T>A, 70-29777T>A, 903-29777T>A
A > T
Intronic
No VIP available CA VA
rs13181 *304T>G, 18123137T>G, 2251A>C, 23927A>C, 45854919T>G, ERCC2 Lys751Gln, ERCC2:2251A>C, ERCC2:Lys751Gln, Lys751Gln, rs13181:T>G
T > G
Missense
Lys751Gln
No VIP available No Clinical Annotations available VA
rs16857540 173900575C>G, 647-92530C>G, 80395721C>G
C > G
Intronic
No VIP available CA VA
rs1695 12658484A>G, 313A>G, 6624A>G, 67352689A>G, GSTP1*2, GSTP1*B, GSTP1: I105V, GSTP1:A313G, GSTP1:I105V, GSTP1:Ile105Val, Ile105Val, Part of haplotypes GSTP1*B and GSTP1*C, rs1695:A>G
A > G
Missense
Ile105Val
No VIP available No Clinical Annotations available VA
rs17116806 1740+8030G>T, 418364G>T, 67945170C>A, 97973252C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs17160359 25379662G>T, 458+6848G>T, 509+6848G>T, 746C>A, 87346819G>T
G > T
Intronic
No VIP available No Clinical Annotations available VA
rs1734787 153325446A>C, 27-27438T>G, 4243384A>C, 42684T>G, 63-27438T>G
A > C
Intronic
No VIP available No Clinical Annotations available VA
rs1734791 153330920A>T, 26+26722T>A, 37210T>A, 4248858A>T, 62+32141T>A
A > T
Intronic
No VIP available CA VA
rs17376848 1896T>C, 475992T>C, 67887542A>G, 97915624A>G, Phe632=, Phe632Phe
A > G
Synonymous
Phe632Phe
No VIP available No Clinical Annotations available VA
rs17431184 102056T>C, 40524715T>C, 802-400T>C, 89720251T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs17435 153311980T>A, 27-13972A>T, 4229918T>A, 56150A>T, 63-13972A>T
T > A
Intronic
No VIP available CA VA
rs17626122 206474012T>C, 2958-6168T>C, 3054-6168T>C, 3075-6168T>C, 56683430T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs1799793 11587G>A, 18135477C>T, 45867259C>T, 862G>A, 934G>A, Asp288Asn, Asp312Asn, XPD Asp312Asn, XPD:Asp312Asn
C > T
Missense
Asp288Asn
No VIP available No Clinical Annotations available VA
rs1799794 -260-1363A>G, -316A>G, 104179267T>C, 7557A>G, 85179267T>C
T > C
5' UTR
No VIP available CA VA
rs1799983 11291734T>G, 12965T>G, 150696111T>G, 894T>G, Asp298Glu, NOS3:894G>T
T > G
Missense
Asp298Glu
No VIP available CA VA
rs1800566 20389C>T, 23359344G>A, 445C>T, 457C>T, 559C>T, 69745145G>A, NQO1*2, NQO1:C609T, NQO1:P187S, NQO1:c.558C>T, Pro149Ser, Pro153Ser, Pro187Ser, rs1800566 C>T
G > A
Missense
Pro149Ser
No VIP available CA VA
rs1801019 124456742G>C, 12530G>C, 30951888G>C, 590G>C, 638G>C, 843G>C, Gly213Ala, OPRT: Gly213Ala
G > C
Not Available
Gly213Ala
No VIP available CA VA
rs1801131 1040A>C, 11208431T>G, 11794419T>G, 1286A>C, 1409A>C, 16685A>C, A1298C, Glu347Ala, Glu429Ala, Glu470Ala, MTHFR:1298A>C
T > G
Not Available
Glu347Ala
rs1801133 11210333G>A, 11796321G>A, 14783C>T, 419C>T, 665C>T, 677C>T, 788C>T, A222V, Ala140Val, Ala222Val, Ala263Val, C677T, MTHFR: c.677C>T, MTHFR:667C>T, p.A222V
G > A
Not Available
Ala140Val
No VIP available CA VA
rs1801158 1490G>A, 1524+33695G>A, 1601G>A, 410195G>A, 97515865C>T, 97981421C>T, Ser497Asn, Ser534Asn
C > T
Not Available
Ser534Asn
No VIP available CA VA
rs1801159 1627A>G, 410221A>G, 67953313T>C, 97981395T>C, DPYD*5, DPYD:A1627G, DPYD:I543V, Ile543Val
T > C
Missense
Ile543Val
No VIP available No Clinical Annotations available VA
rs1801160 129-825C>T, 2194G>A, 620696G>A, 67742838C>T, 97770920C>T, Val732Ile
C > T
Missense
Val732Ile
No VIP available CA VA
rs1801265 42731T>C, 42731T>T, 68320803G>A, 68320803G>G, 85T>C, 85T>T, 98348885G>A, 98348885G>G, Cys29=, DPYD*9A, DPYD:C29R, DYPD:T85C
G > A
Missense
Cys29Arg
No VIP available No Clinical Annotations available VA
rs1870377 1416A>T, 23789A>T, 3312857T>A, 55972974T>A, Gln472His
T > A
Missense
Gln472His
No VIP available No Clinical Annotations available VA
rs1885301 -1549A>G, -1549G>A, 101541053A>G, 3591A>G, 52345517A>G
A > G
5' Flanking
No VIP available CA VA
rs1979277 1303C>T, 1420C>T, 17835470G>A, 18232096G>A, 39761C>T, Leu435Phe, Leu474Phe, SHMT1 L435F
G > A
Missense
Leu435Phe
No VIP available No Clinical Annotations available VA
rs2010851 *1224C>A, 1696642C>A, 1756642C>A
C > A
3' Flanking
No VIP available No Clinical Annotations available VA
rs2010963 -634C>G, -94C>G, 43678350C>G, 43738350C>G, 5398C>G, VEGF-A 405 G/C, VEGFA:405G>C, VEGFA:C405G
C > G
5' UTR
No VIP available No Clinical Annotations available VA
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > T
A > C
Missense
Ser893Ala
Ser893Thr
No VIP available No Clinical Annotations available VA
rs2070474 -80C>G, 1-509G>C, 24891292C>G, 4281861C>G, 5042C>G
C > G
5' UTR
No VIP available CA No Variant Annotations available
rs2070744 -51-762C>T, -786, -813C>T, 11285702C>T, 150690079C>T, 6933C>T, NOS3 -786T>C, NOS3:, T>C, eNOS -786T>C
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs2071559 -906T>C, 3332249A>G, 4397T>C, 55992366A>G
A > G
5' Flanking
No VIP available No Clinical Annotations available VA
rs2072671 20915701A>C, 7595789A>C, 79A>C, CDA: c.79A>C, CDA:79A>C, K27Q, Lys27Gln, p.Lys27Gln
A > C
Missense
Lys27Gln
No VIP available No Clinical Annotations available VA
rs2074087 145799C>G, 16124232C>G, 16184232C>G, 2461-30C>G
C > G
Intronic
No VIP available No Clinical Annotations available VA
rs2236225 1958G>A, 45908845G>A, 59087G>A, 64908845G>A, Arg653Gln, MTHFD1:1958G>A, MTHFD1:Arg653Gln, R653Q
G > A
Missense
Arg653Gln
No VIP available No Clinical Annotations available VA
rs2236722 100801T>C, 115T>C, 22325552A>G, 51534995A>G, Trp39Arg
T > G
T > A
Missense
Trp39Arg
No VIP available No Clinical Annotations available VA
rs2286455 16020162C>T, 70462G>A, 7201959C>T, 759G>A, 786G>A, Ala253=, Ala262=
C > T
Synonymous
Ala262Ala
No VIP available No Clinical Annotations available VA
rs2289310 120476C>A, 30375337G>T, 4442C>A, 79570873G>T, Pro1481Gln
G > T
Missense
Pro1481Gln
No VIP available No Clinical Annotations available VA
rs2291078 1002T>A, 1050T>A, 124458938T>A, 1255T>A, 14726T>A, 30954084T>A, Val350=
T > A
Not Available
Val350Val
No VIP available No Clinical Annotations available VA
rs2293347 187192C>T, 2982C>T, 4858285C>T, 55268916C>T, Asp994=
C > T
Synonymous
Asp994Asp
No VIP available CA VA
rs2297595 226525A>G, 496A>G, 68137009T>C, 98165091T>C, DPYD:496A>G, DPYD:Met166Val, Met166Val
T > C
Missense
Met166Val
No VIP available No Clinical Annotations available VA
rs2305948 17205G>A, 3319441C>T, 55979558C>T, 889G>A, Val297Ile
C > T
Missense
Val297Ile
No VIP available No Clinical Annotations available VA
rs2306283 14089862A>G, 21329738A>G, 388A>G, 50611A>G, Asn130Asp, SLCO1B1*1B
A > G
Missense
Asn130Asp
No VIP available No Clinical Annotations available VA
rs2465403 120090827G>A, 149-11092G>A, 33364376G>A
G > A
Intronic
No VIP available CA VA
rs25487 1196A>G, 16323944T>C, 44055726T>C, Gln399Arg, XRCC1 Arg399Gln, XRCC1:Arg399Gln
T > C
Missense
Gln399Arg
No VIP available CA VA
rs25648 -7C>T, 43678977C>T, 43738977C>T, 534C>T, 6025C>T, Ser178=
C > T
Synonymous
Ser178Ser
No VIP available No Clinical Annotations available VA
rs2669429 105463690A>G, 18737239A>G, 20588T>C, 265-58T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2740574 -392G>A, 37414939C>T, 4713G>A, 5'-flanking region -392A>G, 99382096C>T, CYP3A4*1B, CYP3A4-V, CYP3A4:-392A>G
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs2847153 280-499G>A, 651647G>A, 661647G>A, 9044G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs2854744 -336C>A, 45951075G>T, 45961075G>T, 4797C>A
G > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs2854746 45950645G>C, 45960645G>C, 5227C>G, 95C>G, Ala32Gly
G > C
Missense
Ala32Gly
No VIP available No Clinical Annotations available VA
rs2960436 45967282G>A, 45977282G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs3025039 *171C>T, *237C>T, *253C>T, 19584C>T, 43692536C>T, 43752536C>T, VEGFA:C936T
C > T
3' UTR
No VIP available No Clinical Annotations available VA
rs307805 -942A>G, 180077487T>C, 24888760T>C, 4138A>G
T > C
5' Flanking
No VIP available No Clinical Annotations available VA
rs307822 *1475A>G, 180028717T>C, 24839990T>C, 52908A>G
T > C
3' UTR
No VIP available No Clinical Annotations available VA
rs3110697 10843T>C, 45945029A>G, 45955029A>G, 751-485T>C, 769-485T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs3130 *1078A>G, 120686A>G, 15969938T>C, 7151735T>C
T > C
3' UTR
No VIP available No Clinical Annotations available VA
rs3136228 -152-405T>G, 26831703T>G, 4531T>G, 48009816T>G
T > G
5' Flanking
No VIP available No Clinical Annotations available VA
rs3212948 18192580G>C, 321+74C>G, 45924362G>C, 62725C>G
G > C
Intronic
No VIP available No Clinical Annotations available VA
rs3212986 *197G>T, 1510C>A, 18180954C>A, 45912736C>A, 74351G>T, ERCC1 C8092A, ERCC1:8090C>A, ERCC1:8092C>A, Gln504Lys
C > A
3' UTR
Gln504Lys
No VIP available No Clinical Annotations available VA
rs3218592 111643838C>T, 15813295C>T, 8285G>A, Arg2762Gln
C > T
Missense
Arg2762Gln
No VIP available No Clinical Annotations available VA
rs34116584 241808314C>A, 241808314C>G, 241808314C>T, 32C>A, 32C>G, 32C>T, 5153C>A, 5153C>G, 5153C>T, 999182C>A, 999182C>G, 999182C>T, Pro11Arg, Pro11His, Pro11Leu
C > G
C > T
C > A
Missense
Pro11Arg
Pro11Leu
Pro11His
rs34489327 *145-370delT, *145-370delTinsCTTTAA, *449delA, *449delAinsTTAAAG, *859delT, *859delTinsCTTTAA, 20843delA, 20843delAinsTTAAAG, 6-basepair 3'UTR repeat, 663446delA, 663446delAinsTTAAAG, 673446delA, 673446delAinsTTAAAG, TYMS:-TTAAAG, TYMS:1494del, TYMS:1494del TTAAAG, ttaaag
T > -
T > TTAAAG
3' UTR
rs34743033 28-bp tandem repeats, CCGCGCCACTTGGCCTGCCTCCGTCCCG, TSER*2, TSER*3, TYMS: 28 bp tandem repeat, TYMS: 2R, TYMS: TSER *2/*3, TYMS:TSER 28-basepair 5'UTR enhancer region repeat
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
Not Available
No VIP available No Clinical Annotations available VA
rs351855 1058-90G>A, 11323G>A, 1162G>A, 176520243G>A, 21331516G>A, FGFR4:Arg388, FGFR4:GLY388ARG, Gly388Arg
G > A
Intronic
Gly388Arg
No VIP available No Clinical Annotations available VA
rs3740066 101604207C>T, 3972C>T, 52408671C>T, 66745C>T, ABCC2:3972C>T, I1324I, Ile1324=
C > T
Synonymous
Ile1324Ile
No VIP available No Clinical Annotations available VA
rs3772809 124462824A>G, 1288A>G, 1336A>G, 1541A>G, 18612A>G, 30957970A>G, Ile446Val
A > G
Not Available
Ile446Val
No VIP available No Clinical Annotations available VA
rs3772810 *28A>G, 124462959A>G, 1423A>G, 1676A>G, 18747A>G, 30958105A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs3812718 166909544C>T, 17118962C>T, 25606G>A, 603-91G>A
C > T
Intronic
rs3918290 1905+1G>A, 476002G>A, 67887532C>T, 97915614C>T, DPYD*2A, DPYD:67887533 G>A, DPYD:IVS14 + 1G>A
C > T
Donor
No VIP available No Clinical Annotations available VA
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
No VIP available No Clinical Annotations available VA
rs4243761 26282791G>T, 2717938G>T, 896-11481G>T
G > T
Intronic
No VIP available No Clinical Annotations available VA
rs4426527 1008384A>G, 1020A>G, 14355A>G, 241817516A>G, Ile340Met
A > G
Missense
Ile340Met
No VIP available No Clinical Annotations available VA
rs45445694 2, 28-bp tandem repeats located in the TS enhancer region of 5'UTR, TYMS:*2
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 3
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 7
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 4
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 8
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 9
Not Available
No VIP available No Clinical Annotations available VA
rs45589337 246890A>G, 68116644T>C, 775A>G, 98144726T>C, Lys259Glu
T > C
Missense
Lys259Glu
No VIP available No Clinical Annotations available VA
rs470119 2955A>G, 50966914T>C, 516+27A>G, 552137T>C, 6601A>G
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs4932551 7037485G>C, 92071958G>C
G > C
Not Available
No VIP available No Clinical Annotations available VA
rs4970722 39563T>A, 40-3123T>A, 68323971A>T, 98352053A>T
A > T
Intronic
No VIP available No Clinical Annotations available VA
rs5009910 10070901T>C, 130-33141A>G, 31249014T>C, 315-59846A>G, 70-33141A>G, 903-33141A>G
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs501415 -20+35A>G, 2109706A>G, 54318842A>G
A > G
Intronic
No VIP available CA VA
rs55886062 1679T>G, 410273T>G, 67953261A>C, 97981343A>C, Ile560Ser
A > T
A > C
Missense
Ile560Asn
Ile560Ser
No VIP available No Clinical Annotations available VA
rs56038477 1236G>A, 352197G>A, 68011337C>T, 98039419C>T, Glu412=
C > T
Synonymous
Glu412Glu
No VIP available No Clinical Annotations available VA
rs5906072 45640507T>C, 8492251T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs5934731 447C>T, 7817606C>T, 9935844C>T, Tyr149=
C > T
Synonymous
Tyr149Tyr
No VIP available No Clinical Annotations available VA
rs61764370 *2505T>G, *2626T>G, 18120348A>C, 25360224A>C, 48631T>G
A > C
3' UTR
No VIP available No Clinical Annotations available VA
rs6458232 41569726C>A, 41629726C>A
C > A
Not Available
No VIP available No Clinical Annotations available VA
rs664393 -2021A>G, 10051001T>C, 29071001T>C, 3265A>G
T > C
5' Flanking
No VIP available CA VA
rs67376798 2846A>T, 67519865T>A, 843669A>T, 97547947T>A, Asp949Val
T > A
Missense
Asp949Val
No VIP available No Clinical Annotations available VA
rs6752303 10069372T>C, 130-31612A>G, 31247485T>C, 315-58317A>G, 70-31612A>G, 903-31612A>G
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs6877011 *721G>C, 180029471C>G, 24840744C>G, 52154G>C
C > G
3' UTR
No VIP available No Clinical Annotations available VA
rs7121 *254C>T, *299C>T, 2322C>T, 27674899C>T, 348C>T, 351C>T, 393C>T, 396C>T, 483C>T, 57478807C>T, 69013C>T, Ile116=, Ile117=, Ile131=, Ile132=, Ile774=
C > T
Synonymous
Ile117Ile
No VIP available No Clinical Annotations available VA
rs715171 7223610C>T, 9341848C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs7170769 7035732C>T, 92070205C>T
C > T
Not Available
No VIP available CA VA
rs717620 -24C>T, 101542578C>T, 5116C>T, 52347042C>T, ABCC2: 5'UTR, ABCC2:(-24)C>T, mRNA 118C>T
C > T
5' UTR
No VIP available CA VA
rs7194667 1609-491A>C, 1857097T>G, 31191A>C, 48242898T>G
T > G
Intronic
No VIP available No Clinical Annotations available VA
rs72728438 1974+75A>G, 543742A>G, 67819792T>C, 97847874T>C, IVS15+75, c.1974+75A>G
T > C
Intronic
No VIP available CA VA
rs7325568 21798284C>T, 40818284C>T
C > T
Not Available
No VIP available CA VA
rs75017182 1129-5923C>G, 346167C>G, 68017367G>C, 98045449G>C
G > C
Intronic
No VIP available No Clinical Annotations available VA
rs7608731 10071861T>C, 130-34101A>G, 31249974T>C, 315-60806A>G, 70-34101A>G, 903-34101A>G
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs7664413 102156428C>T, 177608707C>T, 812-33G>A
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs7667298 -271A>G, 3331614T>C, 5032A>G, 55991731T>C
T > C
5' UTR
No VIP available No Clinical Annotations available VA
rs7699188 NC_000004.11, NG_032067.1, NM_001257386.1, NT_016354.19
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs7952081 12630728G>A, 67324933G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs7993418 191205C>T, 28883061G>A, 3639C>T, 9863061G>A, Tyr1213=
G > A
Synonymous
Tyr1213Tyr
No VIP available No Clinical Annotations available VA
rs8071253 -1392C>T, 117+953G>A, 41458619G>A, 63+953G>A, 76184467G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs8175347 233760235_233760236TA[5][6][7][8], 5-TA insertion in promoter, 7-TA insertion in promoter, 8-TA insertion in promoter, UGT1A1*28, UGT1A1*36, UGT1A1*37, microsatellite, short tandem repeat
(TA)6 > (TA)8
(TA)6 > (TA)5
(TA)6 > (TA)7
Not Available
No VIP available No Clinical Annotations available VA
rs833061 -1498C>T, -460, -958C>T, 43677486C>T, 43737486C>T, 4534C>T, VEGF-A -460 C/T, VEGFA:C-460T, VEGFA:T-1498C
C > T
5' Flanking
No VIP available CA VA
rs861539 104165753G>A, 1651-1239G>A, 1782-1239G>A, 21071C>T, 722C>T, 75229G>A, 85165753G>A, Thr241Met
G > A
Intronic
Thr241Met
No VIP available CA VA
rs9344 *1365+4648C>T, 12038G>A, 14768705G>A, 69462910G>A, 723G>A, CCND1 (A870G), CCND1:870G>A, Pro241=, rs603965
G > A
Intronic
Pro241Pro
No VIP available CA VA
rs9561778 3366+1243C>A, 8803391G>T, 95713715G>T, NM_005845.3:c.3366+1243G>T
G > A
G > T
Intronic
No VIP available CA VA
rs9679162 10069401G>T, 130-31641C>A, 31247514G>T, 315-58346C>A, 70-31641C>A, 903-31641C>A
G > T
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
Trade Names
  • 5 Fluorouracil
  • Adrucil
  • Arumel
  • Carac
  • Carzonal
  • Effluderm
  • Efudex
  • Efudix
  • Efurix
  • FU
  • Fluoroblastin
  • Fluoroplex
  • Fluracil
  • Fluracilum
  • Fluri
  • Fluril
  • Fluro Uracil
  • Flurouracil
  • Ftoruracil
  • Kecimeton
  • Phthoruracil
  • Phtoruracil
  • Queroplex
  • Timazin
  • URF
  • Ulup
Brand Mixture Names

PharmGKB Accession Id:
PA128406956

Description

A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid.

Source: Drug Bank

Indication

For the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas, renal cell, and carcinoid.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The precise mechanism of action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5-10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.

Source: Drug Bank

Pharmacology

Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.

Source: Drug Bank

Food Interaction

Vitamin B1 needs increased with long term use.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

8-12%

Source: Drug Bank

Absorption

28-100%

Source: Drug Bank

Half-Life

10-20 minutes

Source: Drug Bank

Toxicity

LD 50=230mg/kg (orally in mice)

Source: Drug Bank

Route of Elimination

Seven percent to 20% of the parent drug is excreted unchanged in the urine in 6 hours; of this over 90% is excreted in the first hour.
The remaining percentage of the administered dose is metabolized, primarily in the liver.

Source: Drug Bank

Chemical Properties

Chemical Formula

C4H3FN2O2

Source: Drug Bank

Isomeric SMILES

c1c(c(=O)[nH]c(=O)[nH]1)F

Source: OpenEye

Canonical SMILES

FC1=CNC(=O)NC1=O

Source: Drug Bank

Average Molecular Weight

130.0772

Source: Drug Bank

Monoisotopic Molecular Weight

130.017855555

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Fluoropyrimidine Pathway, Pharmacodynamics
    Model non-tissue-specific cancer cell displaying genes which may be involved in the pharmacodynamics of the fluoropyrimidines, 5-fluorouracil (5-FU), capecitabine and tegafur.
  1. Fluoropyrimidine Pathway, Pharmacokinetics
    Representation of the metabolic pathways for fluoropyrimidines.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
TYMS (source: Drug Bank)

Drug Interactions

Drug Description
fluorouracil Increases the effect of and toxicity of fluorouacil (source: Drug Bank)
fluorouracil Increases the effect of and toxicity of fluorouacil (source: Drug Bank)
acenocoumarol The antineoplasic agent increases the anticoagulant effect (source: Drug Bank)
acenocoumarol The antineoplasic agent, fluorouracil, may increase the anticoagulant effect of acenocoumarol. (source: Drug Bank)
anisindione The antineoplasic agent, fluorouracil, may increase the anticoagulant effect of anisindione. (source: Drug Bank)
cimetidine Cimetidine increases the effect and toxicity of fluorouracil (source: Drug Bank)
cimetidine Cimetidine increases the effect and toxicity of fluorouracil (source: Drug Bank)
dicumarol The antineoplasic agent increases the anticoagulant effect (source: Drug Bank)
dicumarol The antineoplasic agent, fluorouracil, may increase the anticoagulant effect of dicumarol. (source: Drug Bank)
ethotoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
fosphenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
mephenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
mephenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
metronidazole Risk of 5-FU toxicity when associated with metronidazole (source: Drug Bank)
metronidazole Risk of 5-FU toxicity when associated with metronidazole (source: Drug Bank)
phenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
phenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
warfarin The antineoplasic agent increases the anticoagulant effect (source: Drug Bank)
warfarin The antineoplasic agent, fluorouracil, may increase the anticoagulant effect of warfarin. (source: Drug Bank)
fluorouracil Fluorouracil increases the effect of hydantoin (source: Drug Bank)
fluorouracil Risk of 5-FU toxicity when associated with metronidazole (source: Drug Bank)
fluorouracil Risk of 5-FU toxicity when associated with metronidazole (source: Drug Bank)
fluorouracil Fluorouracil increases the effect of hydantoin (source: Drug Bank)
fluorouracil Fluorouracil increases the effect of hydantoin (source: Drug Bank)
fluorouracil Fluorouracil may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Fluorouracil may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Co-administration of Temsirolimus and Fluorouracil may result in serious adverse drug reactions. (source: Drug Bank)
fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)
fluorouracil The strong CYP2C9 inhibitor, Fluorouracil, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)
fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if fluorouracil is initiated, discontinued or dose changed. (source: Drug Bank)

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Relationships from National Drug File - Reference Terminology (NDF-RT)

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Publications related to fluorouracil: 279

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Polymorphisms in folate-metabolizing enzymes and response to 5-fluorouracil among patients with stage II or III rectal cancer (INT-0144; SWOG 9304). Cancer. 2014. Ulrich Cornelia M, et al. PubMed
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Role of solute carrier transporters in pancreatic cancer: a review. Pharmacogenomics. 2014. Lemstrová Radmila, et al. PubMed
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UGT1A1*28 polymorphisms: a potential pharmacological biomarker of irinotecan-based chemotherapies in colorectal cancer. Pharmacogenomics. 2014. Liu Xiang, et al. PubMed
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The role of IVS14+1 G > A genotype detection in the dihydropyrimidine dehydrogenase gene and pharmacokinetic monitoring of 5-fluorouracil in the individualized adjustment of 5-fluorouracil for patients with local advanced and metastatic colorectal cancer: a preliminary report. European review for medical and pharmacological sciences. 2014. Cai X, et al. PubMed
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Epigenetic perspectives on cancer chemotherapy response. Pharmacogenomics. 2014. Liu Mou-Ze, et al. PubMed
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A Case of 5-FU-Related Severe Toxicity Associated with the p.Y186C DPYD Variant. Clinical pharmacology and therapeutics. 2014. Zaanan A, et al. PubMed
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Response to "A Case of 5-FU-Related Severe Toxicity Associated With the P.Y186C DPYD Variant". Clinical pharmacology and therapeutics. 2014. Offer S M, et al. PubMed
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Pharmacogenomic assessment of cisplatin-based chemotherapy outcomes in ovarian cancer. Pharmacogenomics. 2014. Khrunin Andrey V, et al. PubMed
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Pharmacokinetics, safety, and efficacy of FOLFIRI plus bevacizumab in Japanese colorectal cancer patients with UGT1A1 gene polymorphisms. Journal of clinical pharmacology. 2014. Suenaga Mitsukuni, et al. PubMed
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A rare cause of susceptibility to neutropenic sepsis in a patient with metastatic pancreas cancer. BMJ case reports. 2014. Suarez Martinez-Falero Beatriz, et al. PubMed
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Identification of a candidate single-nucleotide polymorphism related to chemotherapeutic response through a combination of knowledge-based algorithm and hypothesis-free genomic data. Journal of bioscience and bioengineering. 2013. Takahashi Hiro, et al. PubMed
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Tumor angiogenesis genotyping and efficacy of first-line chemotherapy in metastatic gastric cancer patients. Pharmacogenomics. 2013. Scartozzi Mario, et al. PubMed
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Genetic diversity of the KIR/HLA system and outcome of patients with metastatic colorectal cancer treated with chemotherapy. PloS one. 2014. De Re Valli, et al. PubMed
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Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients. PloS one. 2014. Wang Jingbo, et al. PubMed
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Thymidylate synthase genotype-directed chemotherapy for patients with gastric and gastroesophageal junction cancers. PloS one. 2014. Goff Laura W, et al. PubMed
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Pharmacogenetics of ABC and SLC transporters in metastatic colorectal cancer patients receiving first-line FOLFIRI treatment. Pharmacogenetics and genomics. 2013. De Mattia Elena, et al. PubMed
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Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients. Therapeutic drug monitoring. 2013. Teh Lay Kek, et al. PubMed
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ABCC11/MRP8 polymorphisms affect 5-fluorouracil-induced severe toxicity and hepatic expression. Pharmacogenomics. 2013. Magdy Tarek, et al. PubMed
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Common variants in genes coding for chemotherapy metabolizing enzymes, transporters, and targets: a case-control study of contralateral breast cancer risk in the WECARE Study. Cancer causes & control : CCC. 2013. Brooks Jennifer D, et al. PubMed
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Clinical Pharmacogenetics Implementation Consortium Guidelines for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing. Clinical pharmacology and therapeutics. 2013. Caudle Kelly E, et al. PubMed
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ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy. Pharmacogenetics and genomics. 2013. Rumiato Enrica, et al. PubMed
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DPYD IVS14+1G>A and 2846A>T genotyping for the prediction of severe fluoropyrimidine-related toxicity: a meta-analysis. Pharmacogenomics. 2013. Terrazzino Salvatore, et al. PubMed
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Association of common gene variants in the WNT/beta-catenin pathway with colon cancer recurrence. The pharmacogenomics journal. 2013. Páez D, et al. PubMed
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Pharmacogenetic variants in the DPYD, TYMS, CDA and MTHFR genes are clinically significant predictors of fluoropyrimidine toxicity. British journal of cancer. 2013. Loganayagam A, et al. PubMed
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Association of ABCB1 genetic polymorphisms with susceptibility to colorectal cancer and therapeutic prognosis. Pharmacogenomics. 2013. Wu Huizhe, et al. PubMed
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Gender-specific profiling in SCN1A polymorphisms and time-to-recurrence in patients with stage II/III colorectal cancer treated with adjuvant 5-fluoruracil chemotherapy. The pharmacogenomics journal. 2013. Benhaim L, et al. PubMed
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Implications of Genome-Wide Association Studies in Cancer Therapeutics. British journal of clinical pharmacology. 2013. Patel Jai N, et al. PubMed
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Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer. Cancer chemotherapy and pharmacology. 2013. Lee Kyung-Hun, et al. PubMed
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A DPYD Variant (Y186C) in Individuals of African Ancestry Is Associated With Reduced DPD Enzyme Activity. Clinical pharmacology and therapeutics. 2013. Offer S M, et al. PubMed
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Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: the need for further revision of dose and schedule. Internal and emergency medicine. 2013. Magnani Elena, et al. PubMed
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The expression profile of ATP-binding cassette transporter genes in breast carcinoma. Pharmacogenomics. 2013. Hlaváč Viktor, et al. PubMed
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The cyclin D1 (CCND1) rs9344 G>A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy. The pharmacogenomics journal. 2013. Absenger G, et al. PubMed
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The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3'-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients. Pharmacogenetics and genomics. 2013. Sebio Ana, et al. PubMed
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Gender-specific elimination of continuous-infusional 5-fluorouracil in patients with gastrointestinal malignancies: results from a prospective population pharmacokinetic study. Cancer chemotherapy and pharmacology. 2013. Mueller F, et al. PubMed
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MTHFR polymorphisms and capecitabine-induced toxicity in patients with metastatic colorectal cancer. Pharmacogenetics and genomics. 2013. van Huis-Tanja Lieke H, et al. PubMed
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Genetic variability & chemotoxicity of 5-fluorouracil & cisplatin in head & neck cancer patients: a preliminary study. The Indian journal of medical research. 2013. Dhawan Dipali, et al. PubMed
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Dihydropyrimidine Dehydrogenase Gene (DPYD) Polymorphism among Caucasian and non-Caucasian Patients with 5-FU- and Capecitabine-related Toxicity Using Full Sequencing of DPYD. Cancer genomics & proteomics. 2013. Saif Muhammad Wasif. PubMed
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Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines. PloS one. 2013. Jennings Barbara A, et al. PubMed
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SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer. PloS one. 2013. Huang Liu, et al. PubMed
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Contribution of the beta-ureidopropionase (UPB1) gene alterations to the development of fluoropyrimidine-related toxicity. Pharmacological reports : PR. 2012. Fidlerova Julie, et al. PubMed
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PharmGKB summary: very important pharmacogene information for GSTT1. Pharmacogenetics and genomics. 2012. Thorn Caroline F, et al. PubMed
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A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen. The pharmacogenomics journal. 2012. Cecchin E, et al. PubMed
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Intratumoral expression profiling of genes involved in angiogenesis in colorectal cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib). The pharmacogenomics journal. 2012. Wilson P M, et al. PubMed
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An individual coding polymorphism and the haplotype of the SPARC gene predict gastric cancer recurrence. The pharmacogenomics journal. 2012. Winder T, et al. PubMed
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Absence of transcriptomic signature of response to chemotherapy in metastatic colorectal carcinoma patients. Pharmacogenomics. 2012. Laroche-Clary Audrey, et al. PubMed
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Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration. The pharmacogenomics journal. 2012. Fernandez-Rozadilla C, et al. PubMed
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A Systems Biology Approach Identifies SART1 as a Novel Determinant of Both 5-Fluorouracil and SN38 Drug Resistance in Colorectal Cancer. Molecular cancer therapeutics. 2012. Allen Wendy L, et al. PubMed
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Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab. Pharmacogenetics and genomics. 2012. Budai Barna, et al. PubMed
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Genomic approach towards personalized anticancer drug therapy. Pharmacogenomics. 2012. Midorikawa Yutaka, et al. PubMed
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Pharmacogenomics of cisplatin-based chemotherapy in ovarian cancer patients of different ethnic origins. Pharmacogenomics. 2012. Khrunin Andrey, et al. PubMed
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Pharmacogenetic profiling of CD133 is associated with response rate (RR) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), treated with bevacizumab-based chemotherapy. The pharmacogenomics journal. 2012. Pohl A, et al. PubMed
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Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients. Asian Pacific journal of cancer prevention : APJCP. 2012. Dogan Mutlu, et al. PubMed
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Two minor NQO1 and NQO2 alleles predict poor response of breast cancer patients to adjuvant doxorubicin and cyclophosphamide therapy. Pharmacogenetics and genomics. 2011. Jamieson David, et al. PubMed
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Analysis of polymorphisms and haplotype structure of the human thymidylate synthase genetic region: a tool for pharmacogenetic studies. PloS one. 2012. Ghosh Soma, et al. PubMed
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Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6. The oncologist. 2012. Kaldate Rajesh R, et al. PubMed
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Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer. British journal of cancer. 2011. Thomas F, et al. PubMed
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Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis. British journal of cancer. 2011. Tsuji S, et al. PubMed
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Pharmacogenomic characterization of US FDA-approved cytotoxic drugs. Pharmacogenomics. 2011. Peters Eric J, et al. PubMed
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SNPs and Haplotypes in DPYD and Outcome of Capecitabine-Letter. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. van Kuilenburg André B P, et al. PubMed
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The association of polymorphisms in 5-fluorouracil metabolism genes with outcome in adjuvant treatment of colorectal cancer. Pharmacogenomics. 2011. Afzal Shoaib, et al. PubMed
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Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5-fluorouracil. Pharmacological research : the official journal of the Italian Pharmacological Society. 2011. Vignoli Marina, et al. PubMed
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Association of thymidylate synthase enhancer region polymorphisms with thymidylate synthase activity in vivo. The pharmacogenomics journal. 2011. de Bock C E, et al. PubMed
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Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. The pharmacogenomics journal. 2011. Koutras A K, et al. PubMed
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Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas. 2011. Zeng Hongmei, et al. PubMed
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GALNT14 SNP as a potential predictor of response to combination chemotherapy using 5-FU, mitoxantrone and cisplatin in advanced HCC. Pharmacogenomics. 2011. Liang Kung-Hao, et al. PubMed
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TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and -2 clinical trials. The pharmacogenomics journal. 2011. Grimminger P P, et al. PubMed
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EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Hu-Lieskovan Siwen, et al. PubMed
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The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer. Oncology reports. 2011. Kolesar Jill M, et al. PubMed
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VEGF -460T ¿ C polymorphism and its association with VEGF expression and outcome to FOLFOX-4 treatment in patients with colorectal carcinoma. The pharmacogenomics journal. 2011. Chen M-H, et al. PubMed
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Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Deenen Maarten J, et al. PubMed
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Cytidine deaminase single-nucleotide polymorphism is predictive of toxicity from gemcitabine in patients with pancreatic cancer: RTOG 9704. The pharmacogenomics journal. 2011. Farrell J J, et al. PubMed
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Identification of potential pharmacogenomic markers of clinical efficacy of 5-fluorouracil in colorectal cancer. International journal of cancer. Journal international du cancer. 2011. Nobili Stefania, et al. PubMed
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Association analysis of CYP2A6 genotypes and haplotypes with 5-fluorouracil formation from tegafur in human liver microsomes. Pharmacogenomics. 2011. Wang Huijuan, et al. PubMed
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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
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Systems pharmacology assessment of the 5-fluorouracil pathway. Pharmacogenomics. 2011. Muhale Filipe A, et al. PubMed
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Use of a comprehensive panel of biomarkers to predict response to a fluorouracil-oxaliplatin regimen in patients with metastatic colorectal cancer. Pharmacogenomics. 2011. Lamas Maria J, et al. PubMed
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Associations of various gene polymorphisms with toxicity in colorectal cancer patients receiving oral uracil and tegafur plus leucovorin: a prospective study. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2011. Tsunoda A, et al. PubMed
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Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the CYP2A6 polymorphism on pharmacokinetics and clinical activity. British journal of cancer. 2011. Kim K-p, et al. PubMed
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A POLYMORPHISM IN THE CYTIDINE DEAMINASE PROMOTER PREDICTS SEVERE CAPECITABINE-INDUCED HAND-FOOT SYNDROME. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Caronia Daniela, et al. PubMed
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Impact of ABCB1 C3435T polymorphism on lymph node regression in multimodality treatment of locally advanced esophageal cancer. Pharmacogenomics. 2011. Narumiya Kosuke, et al. PubMed
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Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer. The pharmacogenomics journal. 2011. Glimelius B, et al. PubMed
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Pharmacogenetic Tailoring of Irinotecan-based First-line Chemotherapy in Metastatic Colorectal Cancer: Results of a Pilot Study. Anticancer research. 2011. Freyer Gilles, et al. PubMed
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Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells. Chinese medical journal. 2011. Zhang Qiang, et al. PubMed
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Thymidylate Synthase Genotype-Directed Neoadjuvant Chemoradiation for Patients With Rectal Adenocarcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011. Tan Benjamin R, et al. PubMed
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Multiple genetic polymorphisms in the prediction of clinical outcome of metastatic colorectal cancer patients treated with first-line FOLFOX-4 chemotherapy. Pharmacogenetics and genomics. 2011. Huang Ming-Yii, et al. PubMed
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Gender-specific genomic profiling in metastatic colorectal cancer patients treated with 5-fluorouracil and oxaliplatin. Pharmacogenomics. 2011. Gordon Michael A, et al. PubMed
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Pharmacogenetic tests in cancer chemotherapy: what physicians should know for clinical application. The Journal of pathology. 2011. Lee Soo-Youn, et al. PubMed
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Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer. BMC cancer. 2011. Cellier Patrice, et al. PubMed
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Pharmacogenomic contribution to drug response. Cancer journal (Sudbury, Mass.). 2011. Watson Roshawn G, et al. PubMed
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X-Ray Cross-Complementing Group 1 and Thymidylate Synthase Polymorphisms Might Predict Response to Chemoradiotherapy in Rectal Cancer Patients. International journal of radiation oncology, biology, physics. 2010. Lamas Maria J, et al. PubMed
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ABCB1 gene polymorphisms are associated with adverse reactions in fluoropyrimidine-treated colorectal cancer patients. Pharmacogenomics. 2010. Gonzalez-Haba Eva, et al. PubMed
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Three-gene predictor of clinical outcome for gastric cancer patients treated with chemotherapy. The pharmacogenomics journal. 2010. Kim H K, et al. PubMed
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Value of gene polymorphisms as markers of 5-FU therapy response in stage III colon carcinoma: a pilot study. Cancer chemotherapy and pharmacology. 2010. Fariña-Sarasqueta Arantza, et al. PubMed
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Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5-fluorouracil toxicity. Human genetics. 2010. van Kuilenburg André B P, et al. PubMed
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Thymidylate synthase germline polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy based on 5-fluorouracil. Journal of cancer research and clinical oncology. 2010. Páez David, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. Cancer epidemiology. 2010. Henríquez-Hernández Luis Alberto, et al. PubMed
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Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer. International journal of radiation oncology, biology, physics. 2010. Hur Hyuk, et al. PubMed
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Host genetic variants in the IGF binding protein-3 impact on survival of patients with advanced gastric cancer treated with palliative chemotherapy. Pharmacogenomics. 2010. Graziano Francesco, et al. PubMed
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Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010. McLeod Howard L, et al. PubMed
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PharmGKB summary: fluoropyrimidine pathways. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
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Drug transporter pharmacogenetics in nucleoside-based therapies. Pharmacogenomics. 2010. Errasti-Murugarren Ekaitz, et al. PubMed
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Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. The pharmacogenomics journal. 2010. Boni V, et al. PubMed
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Investigation of IVS14 + 1G > A polymorphism of DPYD gene in a group of Bosnian patients treated with 5-Fluorouracil and capecitabine. Bosnian journal of basic medical sciences / Udru¿enje basi¿nih mediciniskih znanosti = Association of Basic Medical Sciences. 2010. Ceri¿ Timur, et al. PubMed
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Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010. Boige Valérie, et al. PubMed
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Human lymphoblastoid cell line panels: novel tools for assessing shared drug pathways. Pharmacogenomics. 2010. Morag Ayelet, et al. PubMed
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Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients. The pharmacogenomics journal. 2010. Khrunin A V, et al. PubMed
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Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients. British journal of clinical pharmacology. 2010. Etienne-Grimaldi Marie-Christine, et al. PubMed
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TaqMan low-density arrays and analysis by artificial neuronal networks predict response to neoadjuvant chemoradiation in esophageal cancer. Pharmacogenomics. 2010. Warnecke-Eberz Ute, et al. PubMed
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Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients. BMC cancer. 2010. Savva-Bordalo Joana, et al. PubMed
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Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study. Breast cancer research : BCR. 2010. Gor Priya P, et al. PubMed
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Genetic polymorphisms associated with 5-Fluorouracil-induced neurotoxicity. Chemotherapy. 2010. Kim Suk-Ran, et al. PubMed
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GSTT1, GSTM1, and GSTP1 polymorphisms and chemotherapy response in locally advanced breast cancer. Genetics and molecular research : GMR. 2010. Oliveira A L, et al. PubMed
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Variants in the dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidylate synthase genes predict early toxicity of 5-fluorouracil in colorectal cancer patients. The Journal of international medical research. 2010. Kristensen M H, et al. PubMed
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Leveraging learning from a phase III colorectal cancer clinical trial: outcomes, methodology, meta-analysis and pharmacogenetics. Transactions of the American Clinical and Climatological Association. 2010. Goldberg Richard M, et al. PubMed
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Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009. Braun Michael S, et al. PubMed
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MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2009. Afzal S, et al. PubMed
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Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients. Journal of human genetics. 2009. Low Siew-Kee, et al. PubMed
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Involvement of N-acetyltransferase human in the cytotoxic activity of 5-fluorouracil. Anti-cancer drugs. 2009. Takubo Kazuko, et al. PubMed
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The increasing role of pharmacogenetics in the treatment of gastrointestinal cancers. Gastrointestinal cancer research : GCR. 2009. Yalçin Suayib. PubMed
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Nitric oxide synthase variants and disease-free survival among treated and untreated breast cancer patients in a Southwest Oncology Group clinical trial. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Choi Ji-Yeob, et al. PubMed
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A highly annotated whole-genome sequence of a Korean individual. Nature. 2009. Kim Jong-Il, et al. PubMed
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MTHFR gene polymorphisms and response to chemotherapy in colorectal cancer: a meta-analysis. Pharmacogenomics. 2009. Zintzaras Elias, et al. PubMed
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TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin. Cancer chemotherapy and pharmacology. 2009. Kim Jong Gwang, et al. PubMed
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Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al. PubMed
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Pharmacogenetic analyses of a phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin: a study of the arbeitsgemeinschaft internistische onkologie. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009. Goekkurt Eray, et al. PubMed
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Dihydropyrimidine dehydrogenase gene variation and severe 5-fluorouracil toxicity: a haplotype assessment. Pharmacogenomics. 2009. Amstutz Ursula, et al. PubMed
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GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. The pharmacogenomics journal. 2009. Alakus H, et al. PubMed
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Pharmacogenetics and biomarkers in colorectal cancer. The pharmacogenomics journal. 2009. Strimpakos A S, et al. PubMed
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Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer. British journal of cancer. 2009. Gusella M, et al. PubMed
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Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer chemotherapy and pharmacology. 2009. Yuan Jianhui, et al. PubMed
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Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer. Cancer research. 2009. DeMichele Angela, et al. PubMed
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C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. European journal of cancer (Oxford, England : 1990). 2009. De Mattia Elena, et al. PubMed
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Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009. Cecchin Erika, et al. PubMed
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Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance. Molecular cancer therapeutics. 2009. Humeniuk Rita, et al. PubMed
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Association of thymidylate synthase variants with 5-fluorouracil cytotoxicity. Pharmacogenetics and genomics. 2009. Peters Eric J, et al. PubMed
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Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine. 2009. Simon Tabassome, et al. PubMed
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Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil. PLoS biology. 2009. Kunz Christophe, et al. PubMed
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Limits to thymidylate synthase and TP53 genes as predictive determinants for fluoropyrimidine sensitivity and further evidence for RNA-based toxicity as a major influence. Cancer research. 2009. Brody Jonathan R, et al. PubMed
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Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxidants & redox signaling. 2009. Kuo Macus Tien. PubMed
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Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology. 2009. Farrell James J, et al. PubMed
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Pharmacogenetics and pharmacogenomics of anticancer agents. CA: a cancer journal for clinicians. 2009. Huang R Stephanie, et al. PubMed
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Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive subgroup?. International journal of clinical oncology / Japan Society of Clinical Oncology. 2008. Iacopetta Barry, et al. PubMed
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Influence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fluoropyrimidine-related toxicity in patients with high-grade toxicity and patients with excellent tolerance of fluoropyrimidine-based chemotherapy. Neoplasma. 2009. Kleibl Z, et al. PubMed
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Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008. Luna-Tortós Carlos, et al. PubMed
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High orotate phosphoribosyltransferase gene expression predicts complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus. Oncology. 2009. Kajiwara Takeshi, et al. PubMed
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ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2009. Hagmann Wolfgang, et al. PubMed
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Predictive Factors for Response and Toxicity in Chemotherapy: Pharmacogenomics. Seminars in colon & rectal surgery. 2008. Sanoff Hanna K, et al. PubMed
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Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. British journal of cancer. 2008. Rouits E, et al. PubMed
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Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy. Journal of cancer research and clinical oncology. 2008. Huang Zhao-Hui, et al. PubMed
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Transcription factor-binding sites in the thymidylate synthase gene: predictors of outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin?. The pharmacogenomics journal. 2008. Paré L, et al. PubMed
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Breast cancer resistance protein expression and 5-fluorouracil resistance. Biomedical and environmental sciences : BES. 2008. Yuan Jian-Hui, et al. PubMed
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Pathway based analysis of SNPs with relevance to 5-FU therapy: relation to intratumoral mRNA expression and survival. International journal of cancer. Journal international du cancer. 2008. Nordgard Silje H, et al. PubMed
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Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. The pharmacogenomics journal. 2008. Ruzzo A, et al. PubMed
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The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. The pharmacogenomics journal. 2008. Capitain O, et al. PubMed
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NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nature genetics. 2008. Fagerholm Rainer, et al. PubMed
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Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
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Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in Chinese cancer patients. Journal of clinical pharmacy and therapeutics. 2008. He Y-F, et al. PubMed
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Pharmacokinetics of 5-fluorouracil in patients heterozygous for the IVS14+1G > A mutation in the dihydropyrimidine dehydrogenase gene. Nucleosides, nucleotides & nucleic acids. 2008. van Kuilenburg A B P, et al. PubMed
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Low expression of gamma-glutamyl hydrolase mRNA in primary colorectal cancer with the CpG island methylator phenotype. British journal of cancer. 2008. Kawakami K, et al. PubMed
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CYP2A6 and the plasma level of 5-chloro-2, 4-dihydroxypyridine are determinants of the pharmacokinetic variability of tegafur and 5-fluorouracil, respectively, in Japanese patients with cancer given S-1. Cancer science. 2008. Fujita Ken-ichi, et al. PubMed
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Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008. Schwab Matthias, et al. PubMed
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The CYP2A6*4 allele is determinant of S-1 pharmacokinetics in Japanese patients with non-small-cell lung cancer. Clinical pharmacology and therapeutics. 2008. Kaida Y, et al. PubMed
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Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008. Lankisch Tim O, et al. PubMed
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Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms and toxicity to capecitabine in advanced colorectal cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008. Sharma Rohini, et al. PubMed
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Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer. Pharmacogenetics and genomics. 2008. Lurje Georg, et al. PubMed
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Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity. Biochemical and biophysical research communications. 2008. Sakamoto Etsuko, et al. PubMed
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Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008. Uhr Manfred, et al. PubMed
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Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacological research : the official journal of the Italian Pharmacological Society. 2008. Nikisch Georg, et al. PubMed
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ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: a preliminary study. BMC cancer. 2008. Huang Ming-Yii, et al. PubMed
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Glutathione S-transferase P1 Ile105Val polymorphism is associated with haematological toxicity in elderly rectal cancer patients receiving preoperative chemoradiotherapy. Drugs & aging. 2008. Agostini Marco, et al. PubMed
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Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy. Journal of experimental & clinical cancer research : CR. 2008. Amstutz Ursula, et al. PubMed
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Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy. Methods in molecular biology (Clifton, N.J.). 2008. Bosch Tessa M. PubMed
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5-Fluorouracil toxicity-attributable IVS14 + 1G > A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients. Pharmacological reports : PR. 2008. Sulzyc-Bielicka Violetta, et al. PubMed
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Strong association of a common dihydropyrimidine dehydrogenase gene polymorphism with fluoropyrimidine-related toxicity in cancer patients. PloS one. 2008. Gross Eva, et al. PubMed
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Genetic regulation of dihydropyrimidinase and its possible implication in altered uracil catabolism. Pharmacogenetics and genomics. 2007. Thomas Holly R, et al. PubMed
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Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. The New England journal of medicine. 2007. Posner Marshall R, et al. PubMed
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Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. The New England journal of medicine. 2007. Vermorken Jan B, et al. PubMed
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DPYD*2A mutation: the most common mutation associated with DPD deficiency. Cancer chemotherapy and pharmacology. 2007. Saif M W, et al. PubMed
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Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity. British journal of clinical pharmacology. 2007. Magné Nicolas, et al. PubMed
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G>C SNP of thymidylate synthase with respect to colorectal cancer. Pharmacogenomics. 2007. Gusella Milena, et al. PubMed
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5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer letters. 2007. Boisdron-Celle M, et al. PubMed
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Genome-wide screening of loci associated with drug resistance to 5-fluorouracil-based drugs. Cancer science. 2007. Ooyama Akio, et al. PubMed
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Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007. Ruzzo Annamaria, et al. PubMed
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Thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) polymorphisms in the Korean population for prediction of 5-fluorouracil-associated toxicity. Therapeutic drug monitoring. 2007. Cho Hyun-Jung, et al. PubMed
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5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity. Cancer research. 2007. An Qian, et al. PubMed
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Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer. Oncology reports. 2007. Salgado Josefa, et al. PubMed
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Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer. Anticancer research. 2007. Tsujie Masanori, et al. PubMed
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Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007. Marguerite Véronique, et al. PubMed
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XRCC1 R399Q polymorphism is associated with response to platinum-based neoadjuvant chemotherapy in bulky cervical cancer. Gynecologic oncology. 2006. Chung Hyun Hoon, et al. PubMed
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Genetic variations and haplotype structures of the DPYD gene encoding dihydropyrimidine dehydrogenase in Japanese and their ethnic differences. Journal of human genetics. 2007. Maekawa Keiko, et al. PubMed
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DPYD*5 gene mutation contributes to the reduced DPYD enzyme activity and chemotherapeutic toxicity of 5-FU: results from genotyping study on 75 gastric carcinoma and colon carcinoma patients. Medical oncology (Northwood, London, England). 2007. Zhang Hong, et al. PubMed
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Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Molecular pharmaceutics. 2007. Collnot Eva-Maria, et al. PubMed
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Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Molecular cancer therapeutics. 2006. Morel Alain, et al. PubMed
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Genomic signatures to guide the use of chemotherapeutics. Nature medicine. 2006. Potti Anil, et al. PubMed
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A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity. Clinical pharmacology and therapeutics. 2006. Bocci Guido, et al. PubMed
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Pharmacogenetics of capecitabine in advanced breast cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Largillier Rémy, et al. PubMed
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FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006. Thussbas Christoph, et al. PubMed
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Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Ichikawa Wataru, et al. PubMed
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The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006. Toffoli Giuseppe, et al. PubMed
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Cancer and leukemia group B gastrointestinal cancer committee. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Goldberg Richard M, et al. PubMed
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Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer research. 2006. Leggas Markos, et al. PubMed
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Impact of P-glycoprotein on clopidogrel absorption. Clinical pharmacology and therapeutics. 2006. Taubert Dirk, et al. PubMed
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Tumor thymidylate synthase 1494del6 genotype as a prognostic factor in colorectal cancer patients receiving fluorouracil-based adjuvant treatment. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006. Dotor Emma, et al. PubMed
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Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics. Pharmacogenetics and genomics. 2006. Martin Yvette N, et al. PubMed
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Inhibitory effect of 5-fluorouracil on cytochrome P450 2C9 activity in cancer patients. Basic & clinical pharmacology & toxicology. 2006. Gunes Arzu, et al. PubMed
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Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition. Expert opinion on drug delivery. 2006. Dey Surajit. PubMed
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Polymorphic tandem repeat sequences of the thymidylate synthase gene correlates with cellular-based sensitivity to fluoropyrimidine antitumor agents. Cancer chemotherapy and pharmacology. 2005. Yawata Ayako, et al. PubMed
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Pharmacogenetics of extraordinary responses to 5-FU/cisplatin chemotherapy in advanced gastric cancer -- report of 2 cases. Onkologie. 2005. Wolschke Christine, et al. PubMed
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Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers. European journal of cancer (Oxford, England : 1990). 2005. Morganti Maria, et al. PubMed
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Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in a cohort of Caucasian individuals. Clinical cancer research : an official journal of the American Association for Cancer Research. 2005. Seck Katharina, et al. PubMed
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Characterization of novel CYP2A6 polymorphic alleles (CYP2A6*18 and CYP2A6*19) that affect enzymatic activity. Drug metabolism and disposition: the biological fate of chemicals. 2005. Fukami Tatsuki, et al. PubMed
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Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). The Journal of pharmacy and pharmacology. 2005. Kobayashi Yasuna, et al. PubMed
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Dihydropyrimidine dehydrogenase deficiency presenting at birth. Journal of inherited metabolic disease. 2005. Al-Sanna'a N A, et al. PubMed
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Multiple organ failure due to 5-fluorouracil chemotherapy in a patient with a rare dihydropyrimidine dehydrogenase gene variant. Onkologie. 2004. Lazar A, et al. PubMed
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Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients. Pharmacogenetics. 2004. Etienne Marie-Christine, et al. PubMed
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Identification of deletion-junction site of CYP2A6*4B allele lacking entire coding region of CYP2A6 in Japanese. Pharmacogenetics. 2004. Ariyoshi Noritaka, et al. PubMed
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Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004. Rouits Elisabeth, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. British journal of cancer. 2004. Stoehlmacher J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Influence of lipid lowering fibrates on P-glycoprotein activity in vitro. Biochemical pharmacology. 2004. Ehrhardt Manuela, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Dihydropyrimidine dehydrogenase pharmacogenetics in the Taiwanese population. Cancer chemotherapy and pharmacology. 2004. Hsiao Hui-Hua, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharmaceutical research. 2004. Hochman Jerome H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms: relationships with 5-fluorouracil sensitivity. British journal of cancer. 2004. Etienne M-C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clinical pharmacology and therapeutics. 2004. Marzolini Catia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of the methylenetetrahydrofolate reductase C677T polymorphism on chemosensitivity of colon and breast cancer cells to 5-fluorouracil and methotrexate. Journal of the National Cancer Institute. 2004. Sohn Kyoung-Jin, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Mutations in exon 14 of dihydropyrimidine dehydrogenase and 5-Fluorouracil toxicity in Portuguese colorectal cancer patients. Genetics in medicine : official journal of the American College of Medical Genetics. 2004. Salgueiro Natália, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected in cancer patients with 5-fluorouracil-related side effects. Human mutation. 2003. Gross Eva, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nature reviews. Cancer. 2003. Ulrich Cornelia M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ferredoxin reductase: pharmacogenomic assessment in colorectal cancer. Cancer research. 2003. Yu Jinsheng, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity. Clinical cancer research : an official journal of the American Association for Cancer Research. 2003. van Kuilenburg André B P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ErbB2 overexpression in human breast carcinoma is correlated with p21Cip1 up-regulation and tyrosine-15 hyperphosphorylation of p34Cdc2: poor responsiveness to chemotherapy with cyclophoshamide methotrexate, and 5-fluorouracil is associated with Erb2 overexpression and with p21Cip1 overexpression. Cancer. 2003. Yang Wentao, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer research. 2003. Kawakami Kazuyuki, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of 5-fluorouracil-inducible target genes using cDNA microarray profiling. Cancer research. 2003. Maxwell Pamela J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of a novel human uridine phosphorylase. Biochemical and biophysical research communications. 2003. Johansson Magnus. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2003. Cohen Victor, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
5-fluorouracil: mechanisms of action and clinical strategies. Nature reviews. Cancer. 2003. Longley Daniel B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional characterization in yeast of genetic variants in the human equilibrative nucleoside transporter, ENT1. Pharmacogenetics. 2003. Osato Douglas H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Genetic polymorphisms of the human MDR1 drug transporter. Annual review of pharmacology and toxicology. 2003. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The contribution of cytochrome P450 to the metabolism of tegafur in human liver. Drug metabolism and pharmacokinetics. 2003. Kajita Jiro, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Evaluation of NQO1 gene expression and variant allele in human NSCLC tumors and matched normal lung tissue. International journal of oncology. 2002. Kolesar Jill M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
High prevalence of the IVS14 + 1G>A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity. Pharmacogenetics. 2002. Van Kuilenburg André B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochimica et biophysica acta. 2002. Banerjee Debabrata, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Implications of dihydropyrimidine dehydrogenase on 5-fluorouracil pharmacogenetics and pharmacogenomics. Pharmacogenomics. 2002. Mattison Lori K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. Journal of the National Cancer Institute. 2002. Stoehlmacher Jan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A novel mutant allele of the CYP2A6 gene (CYP2A6*11 ) found in a cancer patient who showed poor metabolic phenotype towards tegafur. Pharmacogenetics. 2002. Daigo Satoshi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and folate metabolism -- a promising direction. Pharmacogenomics. 2002. Ulrich Cornelia M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines. Cancer research. 2002. Cao Deliang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Profound dihydropyrimidine dehydrogenase deficiency resulting from a novel compound heterozygote genotype. Clinical cancer research : an official journal of the American Association for Cancer Research. 2002. Johnson Martin R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. British journal of cancer. 2001. Iacopetta B, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5'-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls. Clinical cancer research : an official journal of the American Association for Cancer Research. 2001. Raida M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus C, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Low NAD(P)H:quinone oxidoreductase 1 activity is associated with increased risk of acute leukemia in adults. Blood. 2001. Smith M T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001. Villafranca E, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Rapid polyubiquitination and proteasomal degradation of a mutant form of NAD(P)H:quinone oxidoreductase 1. Molecular pharmacology. 2001. Siegel D, et al. PubMed
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Therapeutic drug monitoring of cytotoxic drugs. British journal of clinical pharmacology. 2001. Lennard L. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical implications of dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity: identification of new mutations in the DPD gene. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000. van Kuilenburg A B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug metabolism and disposition: the biological fate of chemicals. 2000. Komatsu T, et al. PubMed
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Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. The pharmacogenomics journal. 2001. Pullarkat S T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Bioactivation of tegafur to 5-fluorouracil is catalyzed by cytochrome P-450 2A6 in human liver microsomes in vitro. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000. Ikeda K, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics. 2000. Collie-Duguid E S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000. van Triest B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. Clinical chemistry. 2000. Van Kuilenburg A B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. The Journal of clinical investigation. 1999. Greiner B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
MTHFR (C677T) polymorphisms and stage III colon cancer: response to therapy. Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology. 1999. Wisotzkey J D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Therapeutic drug monitoring of antimetabolic cytotoxic drugs. British journal of clinical pharmacology. 1999. Lennard L. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone oxidoreductase 1. Pharmacogenetics. 1999. Siegel D, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Human genetics. 1999. Van Kuilenburg A B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual review of pharmacology and toxicology. 1999. Ambudkar S V, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer research. 1999. Kawakami K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects. British journal of clinical pharmacology. 1998. Ridge S A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Characterization of the human dihydropyrimidine dehydrogenase gene. Genomics. 1998. Wei X, et al. PubMed
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Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. European journal of cancer (Oxford, England : 1990). 1998. Miwa M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Human genetics. 1997. Vreken P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et biophysica acta. 1997. Litman T, et al. PubMed
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Preclinical evaluation of CPT-11 and its active metabolite SN-38. Seminars in oncology. 1996. Lavelle F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends in pharmacological sciences. 1995. Gonzalez F J, et al. PubMed
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P-glycoprotein structure and evolutionary homologies. Cytotechnology. 1993. Croop J M. PubMed
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Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. The Journal of clinical investigation. 1988. Diasio R B, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0703-3015-13
DrugBank:
DB00544
PDB:
URF
ChEBI:
46345
KEGG Compound:
C07649
KEGG Drug:
D00584
PubChem Compound:
3385
PubChem Substance:
46508557
7847650
Drugs Product Database (DPD):
2182742
ChemSpider:
3268
HET:
URF
Therapeutic Targets Database:
DAP000829
FDA Drug Label at DailyMed:
e0794add-67a7-4308-93e9-f889472716cc

Clinical Trials

These are trials that mention fluorouracil and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.