- 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
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: UGT1A1 is responsible for the clearance of drugs (e.g., irinotecan) and endbiotic compounds (e.g., bilirubin). Irinotecan's major active and toxic metabolite (SN-38) is inactivated by the UGT1A1 enzyme and then eliminated via the bile. UGT1A1 gene mutations cause accumulation of SN-38, which may lead to irinotecan-related toxicities (neutropenia, diarrhea).
Cause: Variations in TA repeat number in the TATAAA element of the 5' UGT1A1-promoter affects transcription efficiency. The common number of repeats is six [(TA)6, *1 allele], while seven repeats [(TA)7, *28 allele] is associated with reduced transcription activity. Homozygosity for the (TA)7 allele is also associated with Gilbert Syndrome (benign familial hyperbilirubinemia).
Alleles Tested: *36 allele, (TA)5; *1 allele, (TA)6; *28 allele, (TA)7 and *37 allele, (TA)8.
Clinical Sensitivity/Specificity: Risk of irinotecan toxicity by genotype (Br J Cancer (2004) 91:678-82).
6/6 (*1/*1): diarrhea 17 percent; neutropenia 15 percent.
6/7 (*1/*28): diarrhea 33 percent; neutropenia 27 percent.
7/7 (*28/*28): diarrhea 70 percent; neutropenia 40 percent.
Allelic Frequency: *1 (TA)6: Caucasians 0.61, Asians 0.84, African Americans 0.47.
*28 (TA)7: Caucasians 0.39, Asians 0.16, African Americans 0.43.
Methodology: Polymerase chain reaction followed by size analysis using capillary electrophoresis.
Analytical Sensitivity: Greater than 99 percent.
Limitations: Variations in the UGT1A1 gene, other than those targeted, will not be detected. Clinical significance of the rare *36, (TA)5 and *37, (TA)8 alleles in predicting irinotecan toxicities is not well established. Genetic and non-genetic factors other than UGT1A1, may contribute to irinotecan toxicity and efficacy. Diagnostic errors can occur due to rare sequence variations.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0051333||UGT1A1 Genotyping Allele 1||51951-2|
|0051334||UGT1A1 Genotyping Allele 2||51952-0|
|0051335||UGT1A1 Genotyping Interpretation||50398-7|
|2001384||UGT1A1 Genotyping Specimen||31208-2|
- Irinotecan Toxiicity