Retrospective analysis of effect of UGT1A1 polymorphism and non-genetic factors on adverse reactions of irinotecan
OBJECTIVE To explore the gene polymorphism of uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)and non-genetic factors on the irinotecan-related toxicities and improve the clinical dosing safety of irinotecan.METHODS A total of 178 cancer patients on irinotecan-based chemotherapy were enrolled from January 2018 to September 2020.The authors screened UGT1A1 genotype and phenotype,as well as non-genetic factors such as demographic and medication variables,and explored the potential association with irinotecan-related toxicities.RESULTS Clinical types were UGT1A1*6 wild-type(GG,n=110),heterozygous-mutant type(GA,n=61)and homozygous type(AA,n=7).And there were UGT1A1*28 wild-type(TA6TA6,n=148),heterozygous type(TA6TA7,n=27)and homozygous type(TA7TA7,n=3).The metabolizers were extensive(Ems,n=87),intermediate(IMs,n=74)and poor(PMs,n=17).UGT1A1*6 mutation(GA+AA)elevated the inci-dence of severe neutropenia(P=0.021).Phenotypic results indicated that the risk of severe neutropenia in IMs/PMs was signifi-cantly higher than that in EMs(P=0.004).Baseline level of total bilirubin was a risk factor for severe neutropenia(P=0.001)and chemotherapeutic regimen was correlated significantly with severe diarrhea(P=0.004).CONCLUSION Presence of UGT1A 1*6 genetic polymorphism and baseline level of total bilirubin may predict severe myelosuppression of irinotecan.And chemotherapeu-tic regimen is significantly associated with severe diarrhea induced by irinotecan.
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