Relationship between UGT1A1*6/*28 gene polymorphisms and the efficacy and toxicity of irinotecan-based chemotherapy
Authors Bai Y, Wu HW, Ma X, Liu Y, Zhang YH
Received 21 March 2017
Accepted for publication 20 May 2017
Published 19 June 2017 Volume 2017:10 Pages 3071—3081
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Narasimha Reddy Parine
Peer reviewer comments 3
Editor who approved publication: Dr Samir Farghaly
Yu Bai, Hai-wei Wu, Xu Ma, Ying Liu, Yan-hua Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital and Institute, Beijing, People’s Republic of China
Purpose: A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type.
Patients and methods: Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81). Blood samples for detecting UGT1A1 were collected from each patient after various administration regimens.
Results: Colorectal cancer patients with the UGT1A1*6 mutant genotype had a significantly higher risk of severe delayed diarrhea than that of wild-type individuals when administered a CPT-11 dose ≥130 mg/m2 (P=0.042); the same phenomenon was observed when the UGT1A1*6 and UGT1A1*28 mutant genotypes were considered together (P=0.028). However, in lung cancer patients administered a low dose of CPT-11, UGT1A1*6/*28 variants were not significantly associated with severe neutropenia or delayed diarrhea. Furthermore, adult patients with the UGT1A1*6 mutation were more likely to develop severe delayed diarrhea than did wild-type adults (P=0.013); however, the difference was not significant in elderly patients. No significant differences in tumor response were found among the different genotypes (P>0.05).
Conclusion: Thus, age and tumor type influence our ability to predict adverse reactions based on UGT1A1 gene polymorphisms in cancer patients. Further, UGT1A1 gene polymorphisms are not correlated with the efficacy of CPT-11-based regimens.
Keywords: CPT-11, uridine diphosphate glucuronosyltransferase 1A1, SN-38, digital fluorescence molecular hybridization