Gene:
DPYD
dihydropyrimidine dehydrogenase

Available Guidelines

  1. CPIC Dosing Guideline for capecitabine and DPYD
  2. CPIC Dosing Guideline for fluorouracil and DPYD
  3. CPIC Dosing Guideline for tegafur and DPYD
  4. Dutch Pharmacogenetics Working Group Guideline for capecitabine and DPYD
  5. Dutch Pharmacogenetics Working Group Guideline for fluorouracil and DPYD
  6. Dutch Pharmacogenetics Working Group Guideline for tegafur and DPYD

last updated 07/30/2014

CPIC Dosing Guideline for capecitabine 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).

There's more of this guideline. Read more.


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).

There's more of this guideline. Read more.


last updated 07/30/2014

CPIC Dosing Guideline for tegafur 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).

There's more of this guideline. Read more.





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 capecitabine and DPYD

This label is on the FDA Biomarker List
Actionable PGx

Summary

Variants in the DPYD gene (also known as dihydropyrimidine dehydrogenase and DPD) are associated with increased risk for adverse and potentially toxic events, and therefore Capecitabine (Xeloda) is contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency (though genetic testing or screening of DPD activity is not mentioned in the drug label).

There's more of this label. Read more.


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.

There's more of this label. Read more.



Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" 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.

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

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.

? = Mouse-over for quick help

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 Related Drugs?
TheraGuide 5-FU 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 , rs67376798 , 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
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
DPYD ODPM Tox TM DPYD*13, DPYD*2A, DPYD*7 , DPYD D949V
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 on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA *1 N/A N/A N/A
No VIP available No VIP available VA *2A N/A N/A N/A
No VIP available No VIP available VA *3 N/A N/A N/A
No VIP available No VIP available VA *4 N/A N/A N/A
No VIP available No VIP available VA *5 N/A N/A N/A
No VIP available No VIP available VA *7 N/A N/A N/A
No VIP available No VIP available VA *8 N/A N/A N/A
No VIP available No VIP available VA *9A N/A N/A N/A
No VIP available No VIP available VA *9B N/A N/A N/A
No VIP available No VIP available VA *10 N/A N/A N/A
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 No Clinical Annotations available VA
rs12022243 1906-14763G>A, 528836G>A, 67834698C>T, 97862780C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs12132152 67494922G>A, 97523004G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs147545709 2656C>T, 64+2613G>A, 67536073G>A, 827461C>T, 97564155G>A, Arg886Cys
G > A
Intronic
Arg886Cys
No VIP available No Clinical Annotations available VA
rs17116806 1740+8030G>T, 418364G>T, 67945170C>A, 97973252C>A
C > A
Intronic
No VIP available CA VA
rs17376848 1896T>C, 475992T>C, 67887542A>G, 97915624A>G, Phe632=, Phe632Phe
A > G
Synonymous
Phe632Phe
No VIP available CA VA
rs1760217 2623-38806T>C, 64+41452A>G, 67574912A>G, 788622T>C, 97602994A>G
A > G
Intronic
rs1801158 1490G>A, 1524+33695G>A, 1601G>A, 410195G>A, 97515865C>T, 97981421C>T, Ser497Asn, Ser534Asn
C > T
Not Available
Ser534Asn
rs1801159 1627A>G, 410221A>G, 67953313T>C, 97981395T>C, DPYD*5, DPYD:A1627G, DPYD:I543V, Ile543Val
T > C
Missense
Ile543Val
rs1801160 129-825C>T, 2194G>A, 620696G>A, 67742838C>T, 97770920C>T, Val732Ile
C > T
Missense
Val732Ile
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 CA VA
rs2297595 226525A>G, 496A>G, 68137009T>C, 98165091T>C, DPYD:496A>G, DPYD:Met166Val, Met166Val
T > C
Missense
Met166Val
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
rs45589337 246890A>G, 68116644T>C, 775A>G, 98144726T>C, Lys259Glu
T > C
Missense
Lys259Glu
No VIP available No Clinical Annotations available VA
rs4970722 39563T>A, 40-3123T>A, 68323971A>T, 98352053A>T
A > T
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 CA VA
rs67376798 2846A>T, 67519865T>A, 843669A>T, 97547947T>A, Asp949Val
T > A
Missense
Asp949Val
rs72549303 1898delC, 475994delC, 67887540delG, 97915622delG, Pro633Glnfs
G > -
Frameshift
Pro633Gln
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
rs75017182 1129-5923C>G, 346167C>G, 68017367G>C, 98045449G>C
G > C
Intronic
No VIP available No Clinical Annotations available VA
rs7548189 1906-19696G>T, 523903G>T, 67839631C>A, 97867713C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs76387818 67511318G>A, 97539400G>A
G > A
Not Available
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  DPD
PharmGKB Accession Id: PA145

Details

Cytogenetic Location: chr1 : p21.3 - p21.3
GP mRNA Boundary: chr1 : 97543299 - 98386615
GP Gene Boundary: chr1 : 97540299 - 98396615
Strand: minus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Note: The DPYD gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand; therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.

Background

DPYD is the initial and rate limiting enzyme in the three step pathway of uracil and thymidine catabolism and the pathway leading to the formation of beta-alanine. The DPYD protein is responsible for degrading fluoropyrimidines, such as 5-fluorouracil [Article:12164772], capecitabine [Article:15944764], and tegafur [Article:11081569] (see the fluoropyrimidine PK pathway for a diagrammatic representation). Decreased DPYD activity is associated with a greater than four-fold risk of severe or fatal toxicity from standard doses of 5FU [Article:10071185]. Details of specific DPYD variants and their effect on fluoropyrimidine response are discussed below.
Complete DPYD inactivation results in DPYD deficiency with symptoms including epilepsy, motor and mental retardation, and increased urinary levels of uracil and thymine [Article:10071185]. Altered homeostasis of beta-alanine, a structural analog of major inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine, may cause the disturbances in the central nervous system that occur with DPYD deficiency [Article:10071185]. DPYD deficiency is caused by homozygous inactivation of DPYD; heterozygotes tend to be asymptomatic unless challenged, for example by treatment with fluoropyrimidines [Article:10071185].

DPYD gene and regulation

In 1994, Yokota et al. mapped DPYD to the centromeric region of human chromosome 1 between 1p22 and 1q21 [Article:8083224]. Later in 1994 Takai et al. assigned the gene to 1p22 [Article:7713523]. DPYD is expressed in many cell types throughout the body, with liver and peripheral blood being the major sites [Article:3752956]. The gene consists of 23 exons spanning 950kb, resulting in 4399 nucleotides encoding a 1025 amino acid protein. [Articles:8083224, 9721209]
The DPYD gene promoter was mapped in 2000 and several putative transcription factor binding sites were identified including a gamma-interferon responsive element, PEA3, HNF-4, HNF-1 and C/EBP sites [Article:10777676]. The proximal -121bp is sufficient for constitutive activity in Hela and HEK293 cells with transcription factors Sp1 and Sp3 as the transcriptional activators [Articles:11072080, 16806531]. Expression can be induced by phorbol myristate acetate via an AP-1 site between -280 and -290 [Article:15705907]. NSAIDs also appear to have an effect on DPYD expression, and may synergize the effect of 5FU treatment in vivo [Article:19830428].

The DPYD promoter contains several CpG islands and methylation at these locations can regulate transcription in HepG2 cell lines [Article:15501990]. However, methylation differences did not correlate with DPYD mRNA levels in tumor cells [Articles:16778115, 18813836] and is not predictive of 5FU toxicity [Articles:18937829, 20809970].

MicroRNA (miRNA) binding has been shown to negatively regulate expression of DPYD protein [Article:22306127]. Lung tumor samples and cell lines with low expression of the miRNAs miR-27b (MIR27B) and miR-134 (MIR134) had high expression of DPYD protein potentially increasing metabolism of fluoropyrimidines and reducing toxicity or increasing resistance although this has yet to be validated [Article:22306127].

DPYD variation

Patients with less than 70% of the mean observed DPYD protein activity in the normal population are considered at risk for the development of severe toxicity after 5-FU administration PMD: 12209976. Approximately 3-5% of Caucasians have partial DPYD deficiency and 0.2% have complete DPYD deficiency [Article:17121937]. Variation in DPYD protein activity due to gender or race has been investigated although is somewhat contradictory.
Early studies of DPYD protein activity in Caucasians showed no difference between genders or smokers and non-smokers [Article:9723824]. Other studies have shown decreased DPYD activity in women [Articles:7964939, 10027340], with this more pronounced in African Americans than Caucasians [Article:17000684]. African Americans have decreased DPD enzyme activity compared with Caucasians in both sexes [Articles:17000684, 23588312]. Clearance of flurouracil is also decreased in women compared to men [Article:1607921]. Several studies showed increased numbers of women compared to men among patients with fluorouracil toxicity [Articles:11896096, 12209976, 18299612], although in one study this was not significant when excluding patients with breast cancer [Article:12209976]. In one of the largest studies of DPYD variants and fluorouracil toxicity, the variant DPYD was associated with increased risk for toxicity only in males [Article:18299612]. Disease and treatment regimens (which are also related to disease background; breast cancer patients tend to receive bolus fluorouracil whereas colorectal cancer patients tend to receive infusion fluorouracil) may also influence DPYD activity and risk for toxicity.

Several genotypes and haplotypes have been associated with low DPYD activity and fluoruracil toxicity. (These are discussed further with respect to the individual variants).

DPYD and fluoropyrimidine response

DPYD is involved in the metabolism of all the fluoropyrimidines. The oral administration of fluorouracil itself is not feasible due to the high activity of DPYD in the gut wall, which causes rapid metabolism of the drug, and results in decreased and erratic absorption and non-linear pharmacokinetics. Fluorouracil is given by bolus or continuous intravenous infusion or as oral prodrugs such as capecitabine and tegafur. Leukovorin is often given in combination with fluorouracil to stabilize binding of drug metabolite fluorodeoxyuridine monophosphate to TYMS and improve efficacy. Other combinations include enzyme inhibitors such as S-1 which consists of tegafur and two enzyme inhibitors (CDHP 5-chloro-2,4-dihydroxypyridine and OXO, potassium oxonate)[Article:15075664]
Fluorouracil can be given as bolus or continuous infusion. It appears that this influences the flux through different parts of the pharmacokinetic and pharmacodynamic pathways of flurouracil. Bolus treatment results in greater RNA damage whereas continuous treatment results in greater DNA damage [Articles:19383847, 8996164]. Bolus treatment is also associated with higher rates of grade III-IV toxicity [Article:18299612].
Very few studies have examined the role of DPYD variants in efficacy of fluoropyrimidines. A small study of patients with gastric cancer treated with tegafur showed improved survival for those with the *5 allele [Article:18537153]. A study of pancreatic cancer where a portion of the patients were treated with capecitabine, showed decreased survival for those with the AA or AG genotype at rs1760217 [Article:21487324].
There have been several studies of DPYD expression level and response to fluoropyrimidines and low DPYD expression was associated with improved chemotherapy responses [Articles:10778957, 17611699]

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Derek Van Booven, Howard McLeod (CREATE)

Updated by Caroline F. Thorn (08/01/2013).

Variant Summaries rs1801158, rs1801159, rs1801160, rs1801265, rs3918290, rs72549303
Haplotype Summaries DPYD *9B
Drugs
Pathways

Haplotype Overview

Haplotypes for *2A - *10 were extracted from the nomenclature paper [Article:9918128] additional haplotypes are described in [Article:11875367] for *11 and *12 and [Article:11895907] for *13.

Source: PharmGKB

All alleles in the download file are on the positive chromosomal strand. PharmGKB considers the first haplotype listed in each table as the reference haplotype for that set.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Fluoropyrimidine Pathway, Pharmacokinetics
    Representation of the metabolic pathways for fluoropyrimidines.

External Pathways

Links to non-PharmGKB pathways.

  1. Pyrimidine catabolism - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Publications related to DPYD: 112

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Development of a broad-based ADME panel for use in pharmacogenomic studies. Pharmacogenomics. 2014. Brown Andrew Mk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS. Gut. 2014. Rosmarin Dan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014. Rosmarin Dan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients. Therapeutic drug monitoring. 2013. Teh Lay Kek, 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
Clinical Pharmacogenetics Implementation Consortium Guidelines for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing. Clinical pharmacology and therapeutics. 2013. Caudle Kelly E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms of enzymes related to oral tegafur/uracil therapeutic efficacy in patients with hepatocellular carcinoma. Anti-cancer drugs. 2013. Fushiya Nao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer. Breast cancer research and treatment. 2013. Rudek Michelle A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013. Weng Liming, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A discovery resource of rare copy number variations in individuals with autism spectrum disorder. G3 (Bethesda, Md.). 2012. Prasad Aparna, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines. PloS one. 2013. Jennings Barbara 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
Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues. Lung cancer (Amsterdam, Netherlands). 2012. Hirota Takeshi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients. Asian Pacific journal of cancer prevention : APJCP. 2012. Dogan Mutlu, 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
Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer. British journal of cancer. 2011. Thomas 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
Hemizygous deletions on chromosome 1p21.3 involving the DPYD gene in individuals with autism spectrum disorder. Clinical genetics. 2011. Carter 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
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
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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Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas. 2011. Zeng Hongmei, 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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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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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, 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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Global patterns of genetic diversity and signals of natural selection for human ADME genes. Human molecular genetics. 2011. Li Jing, 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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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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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project. The Journal of molecular diagnostics : JMD. 2010. Pratt Victoria M, et al. PubMed
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Can the 2-(13)C-uracil breath test be used to predict the effect of the antitumor drug S-1?. Cancer chemotherapy and pharmacology. 2010. Ishii Yukimoto, 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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
SNPs in genes coding for ROS metabolism and signalling in association with docetaxel clearance. The pharmacogenomics journal. 2010. Edvardsen H, 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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Genetic polymorphisms associated with 5-Fluorouracil-induced neurotoxicity. Chemotherapy. 2010. Kim Suk-Ran, 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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The increasing role of pharmacogenetics in the treatment of gastrointestinal cancers. Gastrointestinal cancer research : GCR. 2009. Yalçin Suayib. PubMed
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Co-inhibition of cyclooxygenase-2 and dihydropyrimidine dehydrogenase by non-steroidal anti-inflammatory drugs in tumor cells and xenografts. Anticancer research. 2009. Réti Andrea, 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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Pharmacogenetics and biomarkers in colorectal cancer. The pharmacogenomics journal. 2009. Strimpakos A S, 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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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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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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Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy. Journal of surgical oncology. 2008. Grau Juan J, 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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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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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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Structural variation of chromosomes in autism spectrum disorder. American journal of human genetics. 2008. Marshall Christian R, 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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Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer: phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044). American journal of clinical oncology. 2007. Jatoi Aminah, 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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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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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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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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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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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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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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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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Correlations between antitumor activities of fluoropyrimidines and DPD activity in lung tumor xenografts. Oncology reports. 2005. Takechi Teiji, 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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Dihydropyrimidine dehydrogenase pharmacogenetics in the Taiwanese population. Cancer chemotherapy and pharmacology. 2004. Hsiao Hui-Hua, et al. PubMed
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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
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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
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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
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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
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Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochimica et biophysica acta. 2002. Banerjee Debabrata, et al. PubMed
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Implications of dihydropyrimidine dehydrogenase on 5-fluorouracil pharmacogenetics and pharmacogenomics. Pharmacogenomics. 2002. Mattison Lori K, et al. PubMed
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Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer cell. 2002. Yeoh Eng-Juh, et al. PubMed
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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
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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
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Therapeutic drug monitoring of cytotoxic drugs. British journal of clinical pharmacology. 2001. Lennard L. PubMed
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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
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The tegafur-based dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines, UFT/leucovorin (ORZEL) and S-1: a review of their clinical development and therapeutic potential. Investigational new drugs. 2000. Hoff P M. PubMed
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Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics. 2000. Collie-Duguid E S, et al. PubMed
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Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. Clinical chemistry. 2000. Van Kuilenburg A B, et al. PubMed
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Therapeutic drug monitoring of antimetabolic cytotoxic drugs. British journal of clinical pharmacology. 1999. Lennard L. PubMed
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Human genetics. 1999. Van Kuilenburg A B, et al. PubMed
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Nomenclature for human DPYD alleles. Pharmacogenetics. 1998. McLeod H L, et al. PubMed
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Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects. British journal of clinical pharmacology. 1998. Ridge S A, et al. PubMed
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Characterization of the human dihydropyrimidine dehydrogenase gene. Genomics. 1998. Wei X, et al. PubMed
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Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Human genetics. 1997. Vreken P, et al. PubMed
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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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Assignment of the human dihydropyrimidine dehydrogenase gene (DPYD) to chromosome region 1p22 by fluorescence in situ hybridization. Genomics. 1994. Takai S, et al. PubMed
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cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria. The Journal of biological chemistry. 1994. Yokota H, et al. 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

Entrez Gene:
1806
OMIM:
274270
612779
UCSC Genome Browser:
NM_000110
RefSeq RNA:
NM_000110
NM_001160301
RefSeq Protein:
NP_000101
NP_001153773
RefSeq DNA:
AC_000044
AC_000133
NC_000001
NG_008807
NT_032977
NW_001838589
NW_921795
UniProtKB:
DPYD_HUMAN (Q12882)
Q96HL6_HUMAN (Q96HL6)
Ensembl:
ENSG00000188641
GenAtlas:
DPYD
GeneCard:
DPYD
MutDB:
DPYD
ALFRED:
LO003560O
HuGE:
DPYD
Comparative Toxicogenomics Database:
1806
ModBase:
Q12882
HumanCyc Gene:
HS06975
HGNC:
3012

Common Searches