UGT1A1 Genotyping - Irinotecan

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Patient who will receive irinotecan in doses >150 mg/m2 with a personal or family history of irinotecan sensitivity, or who has experienced neutropenia while receiving irinotecan
  • Patient suspected to have Gilbert syndrome

Laboratory Testing

  • UGT1A1 (TA) polymorphism genotyping
  • UGT1A1 genotype does not significantly influence risk of irinotecan toxicity when low dose therapy with irinotecan (eg, 15-75 mg/m2 daily for five days for two consecutive weeks) is employed

Irinotecan (CPT-11, Camptosar) is a common chemotherapeutic drug used for the treatment of metastatic colorectal cancer. Allelic variants of UGT1A1 may be associated with increased drug toxicity and with syndromes such as Gilbert syndrome (benign familial hyperbilirubinemia) and Crigler-Najjar syndrome (rare form of nonhemolytic jaundice).


  • Allele frequency in ethnic groups




African Americans

*1 (TA)6




*28 (TA)7





  • The polymorphic TA repeat in the TATA element of the 5’-promoter region of UGT1A1 may consist of 5, 6, 7, or 8 repeats [(TA)5, (TA)6, (TA)7, (TA)8]
    • (TA)6 (also known as UGT1A1*1)  – most common number of repeats
    • (TA)7 (also known as UGT1A1*28)  – important genotype for risk of severe drug-induced toxicity
      • Increase in number of TA repeats may reduce transcription efficiency, lower enzyme concentrations, and lead to accumulation of SN-38 and risk for toxicities
      • Homozygosity for the *28 (TA)7 allele is associated with Gilbert syndrome
    • (TA)5 and (TA)8 alleles are rare but may be clinically significant
      • Number of TA repeats thought to be inversely related to expression of UGT1A1 protein, such that (TA)8 would be associated with the most impaired transcription efficiency


  • Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzyme is responsible for the clearance, by glucuronidation, of drugs (eg, irinotecan) and endogenous substances (eg, bilirubin)
    • >150 functional polymorphisms on UGT1A1 locus
  • SN-38 – primary active and toxic metabolite of irinotecan
    • SN-38 is inactivated by UGT1A1 enzyme to form SN-38G, which is eliminated via bile
  • Variations of the TA repeat length in the UGT1A1 promoter TATA element may lead to decreased gene expression, accumulation of SN-38, and irinotecan-related toxicities
    • Variations of the TA region are associated with Gilbert syndrome
  • Presence of UGT1A1*28 also may affect treatment with the following agents
    • Raloxifene
    • Raltegravir
    • Indinavir
    • Atazanavir
    • Sorafenib

Clinical Presentation

  • Irinotecan toxicity-related symptoms
    • Typically severe (grade 3/4) diarrhea and neutropenia
  • Other related symptoms
    • Nausea, fever, alopecia
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping 0051332
Method: Polymerase Chain Reaction/Fragment Analysis


Variants 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 nongenetic factors other than UGT1A1 may contribute to irinotecan toxicity and efficacy

Diagnostic errors can occur due to rare sequence variations


Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genet Med. 2009; 11(1): 15-20. PubMed

General References

Aiello M, Vella N, Cannavò C, Scalisi A, Spandidos DA, Toffoli G, Buonadonna A, Libra M, Stivala F. Role of genetic polymorphisms and mutations in colorectal cancer therapy (Review). Mol Med Rep. 2011; 4(2): 203-8. PubMed

Di Paolo A, Bocci G, Polillo M, Del Re M, Di Desidero T, Lastella M, Danesi R. Pharmacokinetic and pharmacogenetic predictive markers of irinotecan activity and toxicity. Curr Drug Metab. 2011; 12(10): 932-43. PubMed

Gold HT, Hall MJ, Blinder V, Schackman BR. Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer. Cancer. 2009; 115(17): 3858-67. PubMed

Lee S, McLeod HL. Pharmacogenetic tests in cancer chemotherapy: what physicians should know for clinical application. J Pathol. 2011; 223(1): 15-27. PubMed

Marcuello E, Altés A, Menoyo A, Del Rio E, Gómez-Pardo M, Baiget M. UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer Br J Cancer. 2004; 91(4): 678-82. PubMed

Marques SC, Ikediobi ON. The clinical application of UGT1A1 pharmacogenetic testing: gene-environment interactions. Hum Genomics. 2010; 4(4): 238-49. PubMed

Shulman K, Cohen I, Barnett-Griness O, Kuten A, Gruber SB, Lejbkowicz F, Rennert G. Clinical implications of UGT1A1*28 genotype testing in colorectal cancer patients. Cancer. 2011; 117(14): 3156-62. PubMed

Tzvetkov M, von Ahsen N. Pharmacogenetic screening for drug therapy: from single gene markers to decision making in the next generation sequencing era. Pathology. 2012; 44(2): 166-80. PubMed

Medical Reviewers

Last Update: September 2016