Role Of UUG1A1Polymorphisms (~*28and~*6)in Irinotecan-induced Toxicity In Chinese Cancer Patients

Purpose:The aim was to investigate whether UGT1A1polymorphisms (*28and*6) were associated with toxicity in Chinese cancer patients given irinotecan, and search for other relevant risk factors.Patients and Methods:Chinese cancer patients treated with irinotecan, regardless of diseases and schemes,were enrolled. Detailed data of every patient was collected before and after each cycle of chemotherapy, including routine blood tests. Toxicities were observed and recorded during each cycle of irinotecan treatment and graded according to CTCAE3.0version of the standard terminology of adverse reactions. Genotypes of UGT1A1*28and UGT1A1*6were detected by direct sequencing. All data was statistically analysed with SPSS17.0.Results:Among the32patients, there are18(56.25%) UGT1A1*1/*1double wild genotype (DW),6(18.75%) UGT1A1*1/*28genotype,5(15.625%) UGT1A1*1/*6genotype,3(9.375%) UGT1A1*6/*6homozygous mutation genotype, and neither UGT1A1*28/*28homozygous mutation genotype nor UGT1A1*28/*6double mutant genotype. Severe toxicities were observed in17patients(53%) during the course of chemotherapy, and happened after the first cycle of chemotherapy in8patients (25%). The incidence of Ⅲ-Ⅳ grade leucopenia and neutropenia was increased in UGT1A1*1/*28genotype group compared with the DW group (66.7%VS19.2%, P=0.038; and66.7%VS15.4%, P=0.023,respectively).The incidence of Ⅲ-Ⅳ grade neutropenia in UGT1A1*1/*28plus UGT1A1*6/*6genotype group was much higher than that in DW or UGT1A1*1/*6genotype group. Patients with UGT1A1mutation genotype were more easily to get Ⅲ-Ⅳ grade neutropenia than those with double wild genotype (50%VS5.6%, P=0.01).Conclusions:UGT1A1(include*28and*6) gene polymorphism is associated with severe neutropenia in Chinese cancer patients who accept irinotecan-based chemotherapy. Patients with UGT1A1*28genotype have higher risk to develop Ⅲ-Ⅳ grade leucopenia, and those with UGT1A1*6genotype tend to develop severe neutropenia after the first cycle irinotecan-based chemotherapy. But the incidence of severe delayed diarrhea was not increased in these groups in our study.