Correlation between UGT1A1 polymorphism and efficacy and toxicity of irinotecan in Chinese cancer patients

Shuai Geng ¹ Yulong Shen ¹ Chen Zhang ¹ Nan Wang ² Xinyue Gao ² Xinyu Luo ² Shuai Jiang ^2* Ning Shi ^1*

• ¹ The Ninth Medical Center, Chinese PLA General Hospital, Beijing, China
• ² Harbin Medical University Cancer Hospital, Harbin, China

Objective To assess the association between UGT1A1*6/*28 polymorphisms and Irinotecan (IRI) efficacy/toxicity in Chinese cancer patients. Method We systematically searched PubMed, Cochrane, CNKI, and Wanfang databases. Two investigators independently conducted literature screening, data extraction, and meta-analysis using Revman 5.4. Results This study included 19 clinical trials or case-control studies, with a total of 1698 patients. Meta-analysis showed that, ① There was no correlation between UGT1A1*6 or UGT1A1*28 gene polymorphism and IRI efficacy; ② UGT1A1*6 or UGT1A1*28 gene polymorphisms are associated with grade 3-4 diarrhea, grade 3-4 neutropenia, and grade 3-4 leukopenia, and the above-mentioned toxic reactions are more common in wild types (GG and TA6/6). ③ There was no correlation between UGT1A1*6 and UGT1A1*28 mutations and the efficacy of IRI; ④ The double wild type was more prone to grade 0-2 neutropenia, the single-site variant was more prone to grade 0-2 diarrhea, and the double-site variant was more prone to grade 3-4 neutropenia, but none of them were related to leukopenia.Conclusions UGT1A1*6/*28 polymorphisms predict IRI-induced toxicity severity but not therapeutic efficacy in Chinese patients. These variants may serve as predictive biomarkers for personalized IRI chemotherapy.