UGT1A1 gene polymorphism and irinotecan-induced toxicity in chemotherapy (CT) for colorectal cancer (CRC).

Abstract

e14577 Background: Topoisomerase I inhibitor Irinotecan (IT) is applied in CT for CRC. However, its toxicity associated with polymorphism of TATA box (T-thymine, A-adenine) of the UGT1А1 gene limits its use. Polymorphism of UGT1A1*28 allele induces an increase in TA sequence in gene promoter from 6 to 7. It is associated with inhibition of transcriptional activity and expression of the gene which results in reduction of enzyme activity, increase in time of SN-38 excretion and increase in IT toxicity. Methods: The study included pts with histologically verified CRC, ECOG ≤ 2, normal function of bone marrow, liver and kidneys, without brain metastases, who received IT in the 1st line of CT. Molecular and genetic study of polymorphism of allelic variants 6 and 28 of the UGT1A1 gene was performed with pyrosequencing method. FOLFIRI was used. IT dose was reduced by 25% for patients with high-risk (HR) toxicity. Association between CT toxicity and the UGT1А1 gene polymorphism was assessed. Results: 36 pts (18 m...