The Invader® UGT1A1 Molecular
- 100% accurate as compared to bi-directional sequencing of 285 clinical samples.4
- 98% reproducibility in a multi-center clinical study.4
- Minimal Hands-On Time (<2 hours, including DNA isolation).
- UDP-glucuronosyltransferase 1A1 (UGT1A1) is a polymorphic enzyme responsible for the metabolism of endogenous compounds and drugs, including the chemotherapeutic agent irinotecan (trade name CAMPTOSAR®).1,2
- The most common polymorphism is a variation in the number of TA repeats in the TATA box region of the UGT1A1 gene. The presence of seven TA repeats (UGT1A1*28) instead of the normal six TA repeats (UGT1A1*1) reduces gene expression and results in impaired metabolism. This variant allele is common in many populations, and occurs in 38.7% of Caucasians, 16% of Asians and 42.6% of Africans.1,2
- Studies have shown that impaired metabolism in patients who are homozygous for the UGT1A1*28 allele results in severe, dose-limiting toxicity during irinotecan therapy. These findings led to a recent update in the irinotecan label to include dosing recommendations based on the presence of a UGT1A1*28 allele.3
- Individuals with the UGT1A1*28 allele may require dose modifications for other drugs that are metabolized by the UGT1A1 enzyme.
The Invader® UGT1A1 Molecular Assay
- First IVD pharmacogenetic test using the patented Invader® Chemistry.
- Determines UGT1A1*28 genotype as recommended in the recent label update for the chemotherapeutic irinotecan, which is approved as first-line therapy for metastatic colorectal cancer.
- Identifies patients at risk for severe toxicity when treated with irinotecan therapy.
- Studies ongoing to determine clinical utility for UGT1A1*28 genotyping for new and existing drugs metabolized by UDP glucuronosyltransferase.
||Risk of Neutropenia
||- - -
||10 in 100
|Wildtype *1/*1 Genotype
||0 in 100
|Heterozygous-deficient *1/*28 Genotype
||12 in 100
|Heterozygous-deficient *28/*28 Genotype
||50 in 100
- Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ. Genetic variants in the UDP-glucuronasyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004; 22(8); 1382-1388.
- Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A 1998;95:8170-4.
- The Invader® UGT1A1 molecular assay 510k summary (K051824) (For detailed instructions and equipment specifications, please see the Invader® UGT1A1 Molecular Assay package insert.)
- Camptosar® is a registered trademark of Pfizer Corporation.
- Invader® is a registered trademark of Third Wave Technologies, Inc. All rights reserved. The Invader® chemistry is protected by foreign and domestic patents. ©2007 Third Wave Technologies, Inc.
The Invader® chemistry is protected by foreign and domestic patents.