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Test Catalog

Test ID: DPYDV    
Dihydropyrimidine Dehydrogenase Genotype, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying individuals with genetic variants in DPYD who are at increased risk of toxicity when prescribed 5-fluorouracil (5-FU) or capecitabine chemotherapy treatment

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

5-Fluorouracil (5-FU) and its orally administered prodrug, capecitabine, are fluoropyrimidine-based chemotherapeutic agents that are widely used for the treatment of colorectal cancer and other solid tumors.

 

The dihydropyrimidine dehydrogenase (DPYD) gene encodes the rate-limiting enzyme for fluoropyrimidine catabolism and eliminates over 80% of administered 5-FU. Dihydropyrimidine dehydrogenase (DPYD) activity is subject to wide variability, mainly due to genetic variation. This results in a broad range of enzymatic deficiency from partial (3%-5% of population) to complete loss (0.2% of population) of enzyme activity.(2,3) Patients who are deficient in DPYD are at an increased risk for side effects and toxicity when undergoing 5-FU treatment.(4) In addition, pathogenic homozygous or compound heterozygous variants within DPYD are associated with dihydropyrimidine dehydrogenase (DPD) deficiency. DPD deficiency shows large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation.

 

The following table displays the DPYD variants detected by this assay, the corresponding star allele, and the effect on DPYD enzyme activity. Other or novel variations, besides those listed here, may also impact fluoropyrimidine-related side effects and tumor response.

 

 DPYD Allele

cDNA Nucleotide Change

Effect on Enzyme Activity

*1

None (wild type)

Normal activity

*2A

1905+1G->A

No activity

*7

299_302delTCAT

No activity

*8

703C->T

Probable reduced activity

*9B

2657G->A

Variant of unknown significance

*10

2983G->T

Probable reducedĀ  activity

*11

1003G->T

Probable reduced activity

*13

1679T->G

No activity

rs67376798

2846A->T

Reduced activity

rs75017182

1129-5923C->G

Reduced activity

rs115232898

557A->G

Probable reduced activity

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided. 

 

For additional information regarding pharmacogenomic genes and their associated drugs, see Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Rare genetic variants may be present that could lead to false-negative or false-positive results. Other variants in the primer binding regions can affect the testing, and ultimately, the genotype assessment made.

 

Samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic blood or marrow transplantation, a pretransplant DNA specimen is recommended for testing.

 

Dihydropyrimidine dehydrogenase (DPYD) genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's DPYD status.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Large deletions or rearrangements are not detected by this assay, and these may affect DPYD protein expression and their impact on fluoropyrimidine related side effects and tumor response.

 

This test is not designed to provide specific dosing or drug selection recommendations and is to be used as an aid to clinical decision making only. Drug-label guidance should be used when dosing patients with medications regardless of the predicted phenotype.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Online Mendelian Inheritance in Man: Dihydropyrimidine dehydrogenase deficiency. #274270. Updated 4/18/2012. Available at http://omim.org/

2. Caudle KE, Thorn CF, Klein TE, et al: Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther 2013;94(6):640-645

3. Morel A, Boisdron-Celle M, Fey L, et al: Clinical relevance of different dihyropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 2006 Nov;5(11):2895-2904

4. FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. Accessed June 2017. Available at www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm

5. Offer SM, Fossum CC, Wegner NJ, et al: Comparative functional analysis of DPYD variants of potential clinical relevance to dihydropyrimidine dehydrogenase activity. Cancer Res 2014;74(9):2545-2554

Special Instructions Library of PDFs including pertinent information and forms related to the test