Ordering Recommendation

May be useful in dosage planning for individuals who will receive high-dose irinotecan, have personal or family history of sensitivity to irinotecan, or have experienced neutropenia while receiving irinotecan. Confirms suspected diagnosis of Gilbert syndrome.

Mnemonic
UGT1A1
Methodology

Polymerase Chain Reaction/Fragment Analysis

Performed

Varies

Reported

2-7 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval

By report

Interpretive Data

Background Information for UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping:
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.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81350

Components
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
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Irinotecan Toxiicity
  • UGT1A1
UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping