摘要
为了研究某三甲肿瘤专科医院患者UGT1A1基因型分布,探索真实世界中患者UGT1A1基因多态性与服用伊立替康后的不良反应的相关性,我们回顾性分析2017年5月至2021年12月该院42例接受UGT1A1基因检测的患者资料,总结其中31例服用伊立替康后其血液学以及非血液学不良反应的发生情况。结果表明:UGT1A128基因杂合突变率为21.9%,纯合突变率为4.9%,UGT1A16基因杂合突变率为31.5%,未检测到纯合突变型;本研究中UGT1A16及28杂合突变的患者较野生型患者血液学和非血液学不良反应未见显著性差异,血液学不良反应包括中性粒细胞减少、白细胞减少、血小板减少、血红蛋白减少,非血液学不良反应包括ALT/AST增高、ALP/GGT增高、胆红素增高、乏力、恶心、呕吐、迟发型腹泻;UGT1A16和28双位点突变的患者出现迟发性腹泻的发生率为100%。研究表明,UGT1A16和28双位点杂合突变的患者出现迟发性腹泻风险较高,需引起关注;UGT1A1杂合突变患者应用伊立替康后出现血液学及非血液学不良反应无显著性差异,但需进一步增加样本量证实这一结论。
This study investigated the prevalence of UGT1A1 genotypes in patients at a specialized tertiary tumor hospital and examined the association between UGT1A1 gene polymorphisms and adverse reactions following irinotecan administration in real-world patients.We conducted a retrospective analysis of data from 42 patients who underwent UGT1A1 genetic testing between May 2017 and December 2021 at the hospital.We specifically focused on 31 of these patients,summarizing the occurrence of both hematological and non-hematological adverse reactions after irinotecan treatment.The findings revealed a heterozygous mutation rate of 21.9%for the UGT1A128 gene,a homozygous mutation rate of 4.9%,and a heterozygous mutation rate of 31.5%for the UGT1A16 gene.Notably,no homozygous mutations were detected.Analysis of patients with UGT1A16 and 28 heterozygous mutations showed no significant differences in hematological and non-hematological adverse reactions compared to wild-type patients.Hematological adverse reactions encompassed neutropenia,leukopenia,thrombocytopenia,and anemia,while non-hematological reactions included increased ALT/AST,ALP/GGT,bilirubin,as well as fatigue,nausea,vomiting,and delayed diarrhea.Remarkably,the incidence of delayed diarrhea in patients with UGT1A16 and 28 mutations was 100%,suggesting a higher risk in those with double mutations,warranting increased attention.In conclusion,while no significant differences in adverse reactions were observed between UGT1A1 heterozygous mutation patients and wild-type patients following irinotecan application,it is important to note that further confirmation of these findings is necessary through an expanded sample size.
作者
左靖
孟珺
李超
夏铮铮
唐浩淳
李安娜
马晓芙
Jing Zuo;Jun Meng;Chao Li;Zhengzheng Xia;Haochun Tang;Anna Li;Xiaofu Ma(Department of Pharmacy,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518116,Guangdong,China;School of Pharmacy,Guangdong Medical University,Guangzhou 510089,Guangdong,China)
基金
Chinese Academy of Medical Sciences Oncology Hospital Shenzhen Hospital Youth Initiation Fund Project(Grant No.E010321017)
Guangdong Provincial Health Appropriate Technology Promotion Project(Grant No.202206241503504959)
Pharmaceutical Research Fund of Shenzhen Pharmaceutical Association Hospital(Grant No.sz2022A11)
Special Funding for the Construction of High-level Hospitals in Shenzhen.
