摘要
目的初步了解食管癌人群中尿苷二磷酸葡萄糖醛酸转移酶1A1基因（UGTlAl基因）的多态性分布情况，研究其与伊立替康导致的不良反应（延迟性腹泻和中性粒细胞减少）的相关性。方法纳入2012年1～10月四川省人民医院收治的48例食管鳞状细胞癌患者，男37例、女11例，年龄56（25～38）岁。收集患者食管鳞状细胞癌病理石蜡切片样本，提取基因组DNA，采用聚合酶链反应（PCR）和测序法检测UGTlAl基因的多态性情况，对UGTlAI＊28（TA6〉TA7）、UGTlAI＊6（211G〉A）和UGTlAI＊93（-3156G〉A）3个位点进行考察。观察记录不同UGTlAl基因型患者在伊立替康治疗后出现的不良反应（延迟性腹泻和中性粒细胞减少）情况，并对UGTlAl基因的多态性与不良反应的相关性进行分析。结果48例食管癌患者中有10例携带UGTIAl基因多态性，多态性率为20．8％。其中最常见的是UGTlAI＊93（-3156G〉A）多态性，多态性率为16．7％（8／48）；其次为GTlAI＊6（211G〉A），多态性率为4．2％（2／48）。携带UGTlAl基因多态性的患者在伊立替康治疗发生3～4度腹泻或3～4级中性粒细胞减少症状的比例分别为60．0％和40．0％，显著高于携带野生型UGTlAl基因的患者（21．1％和15．8％，P〈0．05）。有45．5％（5／11）的女性患者携带UGTlAl基因多态性，13．5％（5／37）的男性患者携带UGTlAl基因多态性，两者差异有统计学意义（P〈0．05）。结论在食管癌患者中，UGTlAI＊93（-3156G〉A）和GTlAl；6（211G〉A）两个多态性位点能够有效预测伊立替康导致的不良反应。男性患者UGTlAl的多态性率显著低于女性患者。
Objective To investigate the distribution ofuridine diphosphate-glucuronosyltransferase 1A1 （UGT1A1） gene polymorphisms in esophageal carcinoma （EC） patients, and their relationship with adverse effects （delayed diarrhea and neutropenia） of Irinotecan. Methods Forty-eight patients with esophageal squamous carcinoma who were admitted to Sichuan Provincial People＇s Hospital between January and October 2012 were recruited in the study. There were 37 male and 11 female patients with their age of 56 （25-38） years. Formalin-fixed, paraffin-embedded samples were collected from those EC patients and genomic DNA was extracted. UGT1A1 polymorphisms were detected by PCR and DNA sequencing. Three genetic loci were investigated including UGT1AI＊ 28 （TA6 〉 TA7）, UGT1AI＊ 6 （211G 〉 A）and UGT1AI＊ 93 （-3156G 〉 A）. Adverse effects （delayed diarrhea and neutropenia） of patients with different UGT1A1 polymorphisms after Irinotecan treatment were recorded. The relationship between UGT1A1 polymorphisms and Irinotecan-induced adverse effects was analyzed. Results UGT1A1 polymorphisms were detected in 10 out of 48 （20.8%） EC patients. UGT1AI＊ 93（ 3156G 〉 A）polymorphisms were most common with the polymorphism rate of 16.7% （8/48）, followed by GT1A 1＂ 6 （211G 〉 A ） polymorphisms with the polymorphism rate of 4.2% （2/48）. The incidences of grade 3 ~ 4 diarrhea and grade 3 ~ 4 neutropenia after Irinotecan treatment in the patients with UGT1A1 polymorphisms were 60.0% and 40.0% respec- tively, which were significantly higher than those of the patients with wild type UGTIA1 （21.1% and 15.8% respectively, P 〈 0.05）. UGT1A1 polymorphism rates were 45.5% （5/11 ） in female patients and 13.5% （5/37） in male patients, which were significantly different （P 〈 0.05）. Conclusions In EC patients, 2 polymorphism loci including UGT1AI＊ 93 （ -3156G 〉 A） and GT 1A 1 ＊ 6 （211G 〉 A） can effectively predict adverse effects caused by Irinotecan treatment
出处
《中国胸心血管外科临床杂志》
CAS
2014年第1期52-56,共5页
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
基金
四川省科技厅资助项目(30305020903)~~
