Specimen:

Whole blood

Collection Medium:

Alternate
Collection Media:

Pink top tube (EDTA sprayed), Yellow top tube (ACD solution A)

Minimum:

Adult Preferred Minimum:  3 mL whole blood from lavendar top(EDTA) tube
Adult Absolute Minimum: 1 mL whole blood from lavendar top(EDTA) tube
Pediatric Minimum: 1 mL whole blood from lavendar top(EDTA) tube

Rejection Criteria:

Frozen specimens

Analytic Time:

1 week

Reference Range:

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 UGT1A1 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's 
syndrome (benign familial hyperbilirubinemia).

Alleles detected: (TA)5, (TA)6, (TA)7 and (TA)8.
Clinical Sensitivity/Specificity: The risk of irinotecan toxicity by 
genotype is shown below (based on data from Br J Cancer (2004) 
91:678-82).
    TA genotype          Diarrhea      Neutropenia
      6/6  (*1/*1)          17%            15%
      6/7  (*1/*28)         33%            27%
      7/7  (*28/*28)        70%            40%

Allelic Frequency:
  *1 (TA)6: Caucasians - 61%; Asians - 84%; African Americans - 47%
 *28 (TA)7: Caucasians - 39%; Asians - 16%; African Americans - 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 (TA)5 and 
(TA)8 alleles on risk of irinotecan toxicities is not well established.

Comments:

Please print, complete and submit the following forms to the lab, with 
the specimen and the A-1a Miscellaneous Request:

Patient History for Molecular Genetic Testing

and

Informed Consent for Molecular Genetic Testing from ARUP Laboratories.

Analytical sensitivity:  Greater than 99%

Test
Limitations:

Other polymorphisms or mutation in the UGT1A1 gene will not be 
detected.  Clincial significance of the rare (TA)5 and (TA)8 alleles on 
risk of irinotecan toxicities is not well established.

Methodology:

Polymerase Chain Reaction/Fragment Analysis

CPT Code:

83890, 83898, 83909, 83912