Genetic polymorphisms of the UDP-glucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients.

摘要: Irinotecan often causes unpredictably severe, occasionally fatal, toxicity involving leukopenia or diarrhea. It is converted by carboxyesterase to an active metabolite, SN-38, which further conjugated and detoxified SN-38-glucuronide UDP-glucuronosyltransferase (UGT). We genotyped the UGT1A7 gene direct sequencing analysis polymerase chain reaction-restriction fragment length polymorphism in 118 cancer patients 108 healthy subjects. All had received irinotecan-containing chemotherapy were evaluated see whether variant genotype would increase likelihood of severe irinotecan consisting grade 4 and/or 3 more Among 26 with toxicity, allele frequencies 61.5% for (*)1, 15.4% (*)2, 23.1% (*)3. On other hand, 63.6% 15.8% 20.7% (*)3 among 92 without toxicity. None (*)4. Neither univariate (odds ratio, 1.13; 95% confidential interval, 0.46 - 2.75) nor multivariate logistic regression 0.74; 0.26 2.07) found any significant association between carrying at least one alleles occurrence The distribution genotypes subjects was not significantly different from that (P = 0.99 0.86 those respectively), but less than Caucasians reported previously < 0.001). results suggested determination be useful predicting irinotecan.