Predict risk of dose-related toxicity to 5-FU therapy.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Plasma or serum. Heparinized specimens.
- Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month.
Background information for Dihydropyrimidine Dehydrogenase (DPYD), 3 Variants:
Characteristics:5-Fluorouracil (5-FU) is the most frequently used chemotherapeutic drug for the treatment of many types of cancer, particularly colorectal adenocarcinoma. Grade III-IV drug toxicity attributed to 5-FU occurs in approximately 16 percent of patients, and may include hematologic, gastrointestinal, and dermatologic complications. In some cases, this toxicity can cause death. When 5-FU is metabolized in the body, approximately 80 percent is catabolized by the dihydropyrimidine dehydrogenase (DPD) enzyme. Variants in the DPYD gene can lead to reduced 5-FU catabolism, resulting in the aforementioned toxicity complications.
Inheritance: Autosomal codominant.
Cause: DPYD gene mutations.
DPYD Variants Tested:
Non-functional alleles and toxicity risk:
*13 (rs55886062, c.1679T>G)-Increased risk
*2A (rs3918290, c.1905+1G>A)-Greatly increased risk
c.2846A>T (rs67376798)-Increased risk
A result of negative indicates no variants detected and is predictive of *1 functional alleles and normal enzymatic activity.
Allele Frequency by Population:
*13: Caucasian-0.1 percent; Asian-absent; African American-absent
*2A: Caucasian-0.47-2.2 percent; Asian-absent; African American-absent
c.2846A>T: Caucasians-1.1 percent; Asian-absent; African American-absent
Clinical Sensitivity: Estimated at 31 percent for the DPYD variants analyzed.
Methodology: Polymerase chain reaction(PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Only the targeted DPYD variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. 5-FU drug metabolism, efficacy and risk for toxicity may be affected by genetic and non-genetic factors that are not evaluated by this test. Genotyping does not replace the need for therapeutic drug monitoring or clinical observation.
|Component Test Code*||Component Chart Name||LOINC|
- 5FU drug toxicity
- DPYD genotyping