GTR Home > Tests > UGT1A1 genotyping for irinotecan dosing

Overview

Test name

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UGT1A1 genotyping for irinotecan dosing

Purpose of the test

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This is a clinical test intended for Help: Diagnosis, Monitoring, Mutation Confirmation, Pre-symptomatic, Risk Assessment, Screening

Condition

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1 condition tested. Click Indication tab for more information.

Methodology

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Molecular Genetics
TTargeted variant analysis
PCR electrophoresis, capillary gel

Summary of what is tested

1 genes and variants. Click Methodology tab for more information.

Genes

Clinical validity

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Irinotecan metabolism – Irinotecan is converted in the liver to its active metabolite, SN-38, which subsequently gets conjugated to its glucuronide, SN-38G that is excreted from the body. Decreased levels of glucuronidation results in elevated amounts of SN-38 that is responsible for the severe diarrhea and neutropenia phenotypes in patients. UGT1A1 is involved in the glucuronidation of SN-38 to its glucuronide and the A(TA)7TAA allele has been associated with decreased glucuronidation. Individuals homozygous for the A(TA)7TAA allele are at an elevated risk of developing toxicity phenotypes with irinotecan treatment. The association of the G71R change with Irinotecan metabolism has not been well studied to date.

Citations
  • 1. Bosma et al. “The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome”. (1995) New Engl. J. Med. 333: 1171-1175. 2. Monaghan et al. “Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome”. (1996) Lancet. 347: 578-581. 3. Akaba et al. “Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese”. (1999) J Hum Genet 44(1): 22-5. 4. Iyer et al. “UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity”. (2002) Pharmacogenomics J. 2:43-47. 5. Innocenti et al. “Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan”. (2004) J. Clin. Oncol. 22:1382-1388.

Clinical utility

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Not provided

How to order

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All samples should be shipped via overnight delivery at room temperature. No weekend or holiday deliveries. Label each specimen with the patient’s name, date of birth and date sample collected. Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL Help: http://dnatesting.uchicago.edu/submitting-sample

Test services

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  • Clinical Testing/Confirmation of Mutations Identified Previously
  • Confirmation of research findings
  • Custom Sequence Analysis
  • Custom Prenatal Testing
  • Custom mutation-specific/Carrier testing

Clinical resources

Practice guidelines

  • NACB, 2010
    National Academy of Clinical Biochemistry, Clinical practice considerations. In: Laboratory medicine practice guidelines: guidelines and recommendations for laboratory analysis and application of pharmacogenetics to clinical practice, 2010

Consumer resources

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.