Association Of UGT1A1 Polymorphisms With Irinotecan Induced Toxicities In Advanced Colorectal Cancer: A Meta-Analysis In Asians

Objective: Irinotecan(IRI) has been widely used in advanced colorectal cancer(CRC).However,its use is accompanied by a comparably high incidence of unpredic table severe toxicity.The uridine diphosphate glucuronosyltransferase(UGT) 1A1 is an essential enzyme involved in the complex metabolism of IRI and its activity is regulated by UGT1A1 polymorphisms.Researchers have investigated the effect of U GT1A1*28 and UGT1A1*6 on the IRI-induced toxicities in Asians with colorectal cancer. However, results are both conflicting and difficult to interpret.This meta-ana lysis in Asians was conducted to investigate the possible association of UGT1A1 po lymorphisms with IRI-induced toxic reactions in CRC.Methods: We searched PubM ed,Embase,CNKI,et al to identify eligible studies, extracted data, assessed methodol ogical quality,performed statistical analysis using REVMAN 5.2 and R software and assessed the pooled ORs with 95% CI. Publication bias was evaluated at the sam e time.Results: Ten trials were included.The risk of grade 3~4 neutropenia was hi gher in patients with UGT1A1*28/*28 genotype or UGT1A1*1/*28 genotype than i n those with UGT1A1*1/*1 genotype(OR=3.58,95% CI:1.91~6.71,P<0.0001;OR=1.82,95% CI:1.30~2.54,P=0.0004; respectively).The risk of grade 3~4 d iarrhea was higher in patients with UGT1A1*28/*28 genotype or UGT1A1*1/*28 g enotype than in those with UGT1A1*1/*1 genotype(OR=5.51,95% CI:2.82~10.75,P<0.00001; OR=1.83,95% CI:1.22~2.76,P=0.004;respectively).The risk o f grade 3~4 diarrhea was higher in patients with UGT1A1A/A genotype or UGT1A1G/A genotype than in those with UGT1A1G/G genotype(OR=4.40,95% CI:2.12~9.12,P<0.0001; OR=1.89,95% CI:1.26~2.84,P=0.002;respectively).The risk of grade 3~4 neutropenia was higher in patients with UGT1A1A/A genotype than in those with UGT1A1G/G genotype(OR=2.41,95% CI:1.28~4.55,P=0.007).B ut the risk of grade 3~4 neutropenia was equal between in patients with UGT1A1G/A genotype and in those with UGT1A1G/G genotype(OR=1.32,95% CI:0.96~1.83,P=0.09).Conclusion: UGT1A1*28 polymorphisms or UGT1A1*6 polymorphis ms can predict irinotecan induced grade 3~4 neutropenia and grade 3~4 diarrhea toxicities in Asians’ colorectal cancer.