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Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) and chemotherapy

Posted Apr 18 2011 9:52am

Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) is responsible for bilirubin conjugation with glucuronic acid.Genetic mutations in the UGT1A1 gene may cause reduced or absent UGT1A1 enzymatic activity resulting in hyperbilirubinemia (eg, Gilbert syndrome, Crigler-Najjar syndrome).

There are case reprots suggesting that patients on irinotecan can have severe toxicity if they have a mutaiton of this gene. There are no guidelines that recomemdn routine testing of all patients prior to inrinotecan chemotherapy.

Guilemette C: Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J 2003;3:136-158

2. Innocenti F, Grimsley C, Das S, et al: Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics 2002;12:725-733

3. Costa E, Vieira E, Martins M, et al: Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes. Blood Cells Mol Dis 2006;36:91-97

4. Kitagawa C, Ando M, Ando Y, et al: Genetic polymorphism in the Phenobarbital- responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity. Pharmacogenet Genomics 2005;15:35-41

Oncology: an evidence-based approach By Alfred E. Chang, p.37, 2005

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