UGT1A1 polymorphisms as a pharmacogenetic markers for prediction of irinotecan-induced toxicities in metastatic colorectal cancer

Sa？etak This paper aimed to review the current status of UGT1A1 polymorphisms as a pharmacogenetic marker for prediction of irinotecan-induced toxicities in metastatic colorectal cancer. Deficiencies in the activity uridine diphosphate glucuronosyltransferases (UGT) are mostly due to gene polymorphisms and can lead to increased exposure to irinotecan and its active metabolite causing severe, sometimes life-threatening treatment-related toxicities. Although data suggest that UGT1A1 polymorphisms, especially homozygous (UGT1A1*28/*28, UGT1A1*6/*6) are related to severe irinotecan toxicity and some guidelines highlighted the importance of upfront UGT1A1 genotyping in order to give safer irinotecan dose, UGT1A1 genotyping is currently not being routinely performed in the daily clinical practice. It is important to note that genetic polymorphisms of UGT1A1 show ethnic differences and it is suggested that Caucasian patients should be upfront screened for UGT1A1*28 and Asian patients for UGT1A1*6 as these polymorphisms are common genetic variation in these populations. Data regarding the association of UGT1A1 polymorphisms and treatment response and survival are conflicting. Nevertheless, it is important to think about other genetic variations in the context of chemotherapy-induced toxicities, especially dihydropyrimidine dehydrogenase deficiency (DYPD). In conclusion, UGT1A1 polymorphisms are pharmacogenetic markers which can be used for stratification of patients who are at higher risk of irinotecan-induced toxicities to allow preventive dose reduction to reduce potential toxicities