Relationship between the uridine diphosphate-glucuronosyltransferase 1A1*6 polymorphisms and grade 3-4 neutropenia and diarrhea induced by irinotecan: a Meta-analysis

Abstract

Objective To evaluate the relationship between the uridine diphosphate-glucuronosyl-transferase 1A1 (UGT1A1)*6 polymorphisms and grade 3-4 neutropenia and diarrhea induced by irinotecan. Methods The databases of PubMed, Science Direct, Wiley Online Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database and VIP from the inception to January 15, 2015 were searched. The clinical research papers which were about the relationship between the UGT1A1*6 polymorphisms and grade 3-4 neutropenia and diarrhea induced by irinotecan were collected. The quality of methodology in enrolled papers were evaluated. The software Review Manager 5.3 was used for Meta-analysis. The evaluating indicators of the relationship between UGT1A1*6 and the adverse reactions of irinotecan were odds ratio (OR) and 95% confidence interval (CI). Results A total of 14 papers were enrolled into this Meta-analysis. The numbers of papers in Chinese and English were 5 and 9, respectively and all the papers were from Asian countries. The result of Begg test showed that there were no obvious publication bias in the enrolled papers. The results of Meta-analysis showed that compared with the patients who carried UGT1A1*1/*1 (wild type), the risk of grade 3-4 neutropenia induced by irinotecan in the patients who carring UGT1A1*6/*6 (homozygous mutation) was significantly increased (OR=3.01, 95%CI: 2.01-4.50, P<0.000 01). Compared with the patients who carried UGT1A1*1/*1 (wild type), the risk of grade 3-4 diarrhoea induced by irinotecan in the patients carring UGT1A1*6/*6 (homozygous mutation) and the patients carring UGT1A1*1/*6 (heterozygous mutation) were significantly increased (OR=3.79, 95%CI: 2.38-6.04, P<0.000 01; OR=1.68, 95%CI: 1.16-2.42, P=0.006). Conclusions The polymorphisms of UGT1A1*6 are associated with grade 3-4 neutropenia and diarrhea induced by irinotecan. The risk of grade 3-4 neutropenia due to irinotecan in the patient carring UGT1A1*6 homozygous mutation is increased. The risk of grade 3-4 diarrhoea induced by irinotecan in the patients carring UGT1A1*6 homozygous mutation and heterozygous mutation is increased. Key words: Irinotecan; Neutropenia; Diarrhea; Uridine diphosphate-glucuronosyltransferase