UGT1AI*6 and UGT1A1*27 for individualized irinotecan chemotherapy.

Genetic polymorphisms of uridine 5'-diphospho-glucuronosyl-transferase (UGT)1A1, a crucial drug-metabolizing enzyme of the anticancer drug irinotecan, are essential determinants of individual variation in susceptibility to irinotecan-related toxicity. The FDA has revised the package insert of irinotecan in order to warn of the association between toxicity and UGTIA128, a variant sequence in a promoter region of the UGTIA1 gene. Unlike UGT1A128, UGT1AI6 and UGTIA127 polymorphisms are found in a coding region of the gene, and are known to directly reduce the activity of the UGT enzyme. Therefore, it is reasonable to assume that the presence of UGT1A16 or UGTIA127 would also increase the risk of irinotecan toxicity. Importantly, UGTIA16 and UGT1Al27 have only been identified in the Asian population. Although conclusive evidence linking UGTIAI6 and/or UGT1Al27 to irinotecan toxicity is insufficient at this time, these variants should be tested in addition to UGTIA1*28 for more individualized irinotecan chemotherapy, especially among the Asian population.