UGT1A1基因多态性与伊立替康所致不良反应的相关性分析

Association of UGT1A1 Gene Polymorphisms with Adverse Reactions Caused by Irinotecan

目的:研究本院肿瘤患者UGT1A1基因多态性分布,探讨UGT1A1基因多态性与伊立替康所致不良反应的相关性。方法:回顾性分析2016~2018年就诊于本院并接受伊立替康治疗的肿瘤患者UGT1A1基因多态性分布,分析用药后不良反应发生情况,比较不同基因型之间的差异。结果:共计76例肿瘤患者被纳入分析。76例患者均行UGT1A1*28基因检测(突变比率23.68%),其中有45例患者同时行UGT1A1*6基因检测(突变比率24.44%)。UGT1A1*28基因突变患者发生Ⅲ~Ⅳ度白细胞减少的风险显著高于野生型(OR=10.79,95%CI:1.24~93.86, P=0.016)。伊立替康化疗引起的其他不良反应,包括血小板减少、中性粒细胞减少、腹泻、肝损伤在本研究中未显示出与UGT1A1基因型的显著相关性(P>0.05)。结论:UGT1A1*28基因多态性与伊立替康引起的严重白细胞减少相关。

Objective: To study the distribution of UGT1 A1 gene polymorphisms in cancer patients of a tertiary hospital and its relationship with the adverse reactions caused by irinotecan. Methods: The distribution of UGT1 A1 gene polymorphiams as well as the toxicity after treatment with irinotecan-based regimen in cancer patients from Jan 2016 to Dec 2018 were retrospectively analyzed. The differences of UGT1 A1 genotypes on the toxicity of irinotecan were fully studied. Results: A total of 76 patients were enrolled. UGT1 A1*28 genotype was tested in all patients with mutation rate of 23.68% and UGT1 A1*6 genotype was tested in 45 patients with mutation rate of 24.44%. The risk of grade 3 or 4 of leukopenia in patients with UGT1 A1*28 mutation was higher than that of wild type(OR=10.79, 95% CI: 1.24-93.86,P=0.016). However, there was no obvious relevance between UGT1 A1 genotype and other adverse reactions such as thrombocytopenic, neutropenia, diarrhea and hepatic injury caused by irinotecan(P >0.05).Conclusion: UGT1 A1*28 polymorphism may associate with severe leukopenia caused by irinotecan.