Dihydropyrimidine Dehydrogenase (DPYD), 3 Variants

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. 

Please note the information contained in this report does not contain medication recommendations, and should not be interpreted as recommending any specific medications. Any dosage adjustments or other changes to medications should be evaluated in consultation with a medical provider.