The relationship between UGT1A1 gene polymorphisms and the toxicity and efficacy of irinotecan-based chemotherapy in advanced colorectal cancer

ZHANG Yong; SU Dan; ZHANG Ting-ting; MAO Zhi-yuan; BAI Li

Abstract：Objective:To evaluate the correlations between UGT1A1*28/*6 gene polymorphisms and irinotecan-associated toxicity and efficacy in treatment of advanced colorectal cancer. Methods: The UGT1A1*28/*6 genotypes of 102 advanced colorectal cancer patients treated in our department from June 2011 to June 2013 were detected. The toxicity and efficacy were observed and recorded after irinotecan-based chemotherapy. The difference of toxicity and efifcacy among patients with different genetic polymorphisms were assessed. Results:There was no signiifcant difference in the incidence of Grade 3-4 neutropenia and delayed-onset diarrhea among the patients with different UGT1A1*28 and UGT1A1*6 genotypes. When UGT1A1*28/*6 genotypes were analyzed simultaneously, the patients with double allele mutations had signiifcantly higher incidence of Grade 3-4 neutropenia than those with single allele mutation or wild type (57.1%, 17.4%, 4.3%, respectively;Fisher's exact test P=0.005;Cochran-Armitage trend test P=0.002). UGT1A1*28 genotype had no effect on response rate (RR) and disease control rate (DCR), while the patients with UGT1A1*6 mutation showed worse efficacy (RR and DCR) than those with wild genotype (P= 0.023, P= 0.032). When conjoint analysis of the effect of UGT1A1*28/*6, the differences of RR and DCR were signiifcant in patients with wild type, single and double allele mutation (Fisher's exact test P=0.002,P=0.008), and DCR had a decreased trend with the increase of mutant alleles (95.7%, 73.9%, 42.9%, respectively;Cochran-Armitage trend test P=0.001). Conclusion:Joint detection of UGT1A1*28 and UGT1A1*6 genotype is of more value in prediction of irinotecan-related toxicity and efifcacy than single allele detection.