Correlation analysis between UGT1A1 gene polymorphism,and the toxicity and efficacy of irinotecan in the treatment of advanced gastrointestinal cancer

Objective:To investigate the correlations between uridine-diphosphoglucuronate glucuronosyltransferase 1 family polypetide A1(UGT1A1) gene polymorphism,and the toxicity and efficacy of irinotecan in the treatment of advanced gastrointestinal cancer.Methods:The UGT1A1 genotypes in 62 advanced gastrointestinal cancer patients before treatment with irinotecan were detected using the polymerase chain reaction and high-resolution melting analysis.The correlations between UGT1A1 gene polymorphisms,and the toxicity and efficacy of irinotecan were analyzed.Results:The distribution frequency of wild-type(TA6/6),heterozygous mutant-type(TA6/7) and homozygous mutant-type(TA7/7) in UGT1A1*28 loci were 77.4%,11.3%,and 11.3%,respectively.The proportion of wild-type(G/G),heterozygous mutant-type(G/A) and homozygous mutant-type(A/A) in UGT1A1*6 loci were 79.1%,16.1% and 4.8%,respectively.Compared with the wild types of UGT1A1*28 and UGT1A1*6,the risks of the more than grade 3 diarrhea and neutropenia in mutant types of UGT1A1*28 and UGT1A1*6 increased(P<0.05 to P<0.01).The difference of the efficacy between different genotypes of UGT1A1 was not statistically significant(P>0.05).Conclusions:During the irinotecan in the treatment of advanced gastrointestinal cancer,the locus mutations of UGT1A1*28 and UGT1A1*6 can be regarded as the predictors of irinotecan-associated severe delayed diarrhea and neutropenia.The correlation between UGT1A1 gene polymorphism and efficacy of irinotecan is not found.