Distribution of the UGT1A1*28 polymorphism in Caucasian and Asian populations in the US: a genomic analysis of 138 healthy individuals.

The hepatic isoform 1A1 of uridine diphosphate glucuronosyltransferase is responsible for glucuronidation and detoxification of SN-38, the active metabolite of irinotecan. The presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter leads to a significant decrease in SN-38 glucuronidation. Patients with the UGT1A1 (TA)7 allele are more likely to experience severe neutropenia and diarrhea following irinotecan chemotherapy.

Quantitation of dihydropyrimidine dehydrogenase (DPD) mRNA expression levels in normal colon and colorectal cancer tumor paraffin-embedded tissue specimens.

5-Fluorouracil (5-FU) has been used for more than 40 years in the treatment of neoplastic disease, and remains the standard first-line treatment for colorectal cancer in combination with irinotecan and leucovorin. Previous studies indicated that measurement of dihydropyrimidine dehydrogenase (DPD) gene expression before treatment was valuable in determining the potential benefit of and toxicity to 5-FU treatment. In this study, we investigated the association between intratumoral DPD gene expression and the adjacent normal tissue DPD gene expression and DPD mRNA expression level in non-paired colon tumor and normal colon tissue specimens.