Irinotecan is an anti-cancer agent that is used for the treatment of metastatic carcinoma of the colon or rectum. Although it prolongs survival, it causes severe (grade 3-4) diarrhea and neutropenia in approximately 20-35% of patients treated. The ability to predict patients who will eventually suffer these potentially fatal toxicities is an important consideration when using irinotecan.
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. UGT1A1 is involved in the glucuronidation of SN-38 to its glucuronide. Decreased levels of glucuronidation results in elevated amounts of SN-38 that is responsible for the severe diarrhea and neutropenia phenotypes in patients. Individuals homozygous for the A(TA)7TAA allele are at an elevated risk of developing toxicity phenotypes with irinotecan treatment