Yang Yuwei, Zhou MengMeng, Hu Mingjun, Cui Yanjie, Zhong Qi, Liang Ling, Huang Fen
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
Asia Pac J Clin Oncol. 2018 Oct;14(5):e479-e489. doi: 10.1111/ajco.13028. Epub 2018 Jun 22.
Previous articles explored the role of UGT1A1 polymorphism on predicting irinotecan-induced toxicity, but the conclusions were still inconsistent and not comprehensive. We performed this meta-analysis to investigate the association between UGT1A1 polymorphism and irinotecan-induced toxicity.
PubMed and Web of Science were searched for articles before July 2017. Inclusion and exclusion criteria were set to select eligible articles, and corresponding data were extracted from those articles. Subgroup analyses based on different cancer categories, doses and races were carried out to achieve comprehensive results. Statistical analyses were conducted using STATA 11.0.
A total of 38 studies with 6742 cases were included after reading full text. Both UGT1A16 and UGT1A128 polymorphism are significantly associated with severe irinotecan-induced toxicity. Both Asian and Caucasian cancer patients with UGT1A128 variant had an increased risk. Compared with heterozygous variant, patients with homozygous variant suffered from a higher risk of toxicity. The effect of UGT1A128 polymorphism on diarrhea was less than on neutropenia. Subgroup analysis exhibited that for UGT1A16 polymorphism, patients treated with low-dose irinotecan were at a notable risk of toxicity. Moreover, the association between UGT1A16 polymorphism and irinotecan-induced toxicity was found in patients suffering from respiratory system cancers.
Both UGT1A16 and UGT1A128 polymorphisms can be considered as predictors of irinotecan-induced toxicity, with effect varying by race, cancer type and irinotecan dose.
既往文章探讨了UGT1A1基因多态性在预测伊立替康所致毒性方面的作用，但结论仍不一致且不全面。我们进行了这项荟萃分析以研究UGT1A1基因多态性与伊立替康所致毒性之间的关联。
检索了PubMed和Web of Science中截至2017年7月的文章。设定纳入和排除标准以选择合格文章，并从这些文章中提取相应数据。基于不同癌症类别、剂量和种族进行亚组分析以获得全面结果。使用STATA 11.0进行统计分析。
阅读全文后共纳入38项研究，6742例病例。UGT1A16和UGT1A128基因多态性均与伊立替康所致严重毒性显著相关。携带UGT1A128变异的亚洲和白种癌症患者风险增加。与杂合变异患者相比，纯合变异患者毒性风险更高。UGT1A128基因多态性对腹泻的影响小于对中性粒细胞减少的影响。亚组分析显示，对于UGT1A16基因多态性，接受低剂量伊立替康治疗的患者毒性风险显著增加。此外，在患有呼吸系统癌症的患者中发现了UGT1A16基因多态性与伊立替康所致毒性之间的关联。
UGT1A16和UGT1A128基因多态性均可被视为伊立替康所致毒性的预测指标，其作用因种族、癌症类型和伊立替康剂量而异。
