UGT1A1*28和UGT1A1*6基因多态性与伊立替康不良反应的关系  

Relationship between UGT1A1*28 and UGT1A1*6 gene polymorphism and adverse reactions of irinotecan-based chemotherapy

作　　者：张勇[1] 苏丹[1] 郭晓川[1] 房慧[1] 白莉[1] 

机构地区：[1]解放军总医院肿瘤内科,北京100853

出　　处：《解放军医学院学报》2014年第5期489-492,495,共5页Academic Journal of Chinese PLA Medical School

摘　　要：目的探讨UGT1A1＊28和UGT1A1＊6基因多态性在中国人中的分布，并评价其与伊立替康不良反应之间的关系。方法收集2011年3月－2012年3月在我科住院治疗的158例恶性肿瘤患者的外周血，检测其UGT1A1＊28和UGT1A1＊6基因型，其中132例使用伊立替康方案化疗，比较不同基因型患者的不良反应差异。结果158例中，UGT1A1＊28野生型TA6／6者126例（79．7％），杂合突变型TA6／7者30例（19．O％），纯合突变型TA7／7者2例（1．3％）；64例进行UGT1A1＊6基因检测，G／G野生型40例（62．5％），G／A杂合突变型23例（35．9％），A／A纯合突变型1例（1．6％）。UGT1A1＊28基因突变可增加2～4级迟发性腹泻发生率（TA6／6者15．0％、TA6／7者34．8％、TA7／7者50．0％，P=0．000）；联合UGT1A1＊28和UGT1A1＊6基因型，野生型（TA6／6且G／G）患者发生2～4级迟发性腹泻和3～4级中性粒细胞减少的概率明显低于单点变异型和双点变异型（13．0％、22．2％、100．0％，P=0．004；8．7％、25．9％、66．7％，P=0．045）。结论UGT1A1＊28和UGT1A1＊6基因突变患者使用含伊立替康化疗方案时不良反应发生率较高。与单一检测一个位点相比，联合检测UGT1A1＊28和UGT1A1＊6基因型能更准确地预测伊立替康不良反应。Objective To assess the correlation of UGT1A1＊28 and UGT1A1＊6 gene polymorphism with adverse reactions of irinotecan-based chemotherapy by analyzing the distribution of UGTIA1 gene polymorphism in Chinese people. Methods Peripheral blood samples were taken from 158 malignant tumor patients admitted to our hospital from March 2011 to March 2012. Their UGT1A1 ＊28 and UGT1A1 ＊6 genotypes were detected by direct sequencing. Of the 158 patients, 132 received irinotecan chemotherapy. The adverse reactions to irinotecan chemotherapy were compared in patients with different genotypes. Results Among the 158 patients with UGT1A1＊28 gene, wild genotype TA6/6, heterozygotic mutation genotype TA6/7, and homozygotic mutation genotype TA7/7 were detected in 126 （79.7%）, 30 （19.0%）, and 2 （1.3%） patients, respectively. Among the 64 patients with UGT1A1 ＊6 gene, wild genotype G/G, heterozygotic mutation genotype G/A, and homozygotic mutation genotype A/A were detected in 40 （62.5%）, 23 （35.9%）, and 1 （1.6%） patients, respectively. The incidence of grades 2-4 delayed diarrhea was lower in patients with wild genotype TA6/6 than in those with wild genotypes TA6/7 andTA7/7 （15.0% vs 34.8% and 50.0%, P=0.000）. The incidence of grades 3-4 neutropenia was significantly lower in patients with wild genotypes TA6/6 and G/G than in those with a heterozygotic or homozygotic mutation genotype or with both heterozygotic and homozygotic mutation genotypes （13.0% vs 22.2% and 100.0%, P=0.004 ; 8.7% vs 25.9% and 66.7%, P=0.045）. Conclusion The incidence of adverse reactions to irinotecan chemotherapy is high in patients with UGT1A1＊ 28 and UGT1A1＊6 gene mutations. Detection of UGT1A1＊28 and UGT1A1＊6 genotypes can more accurately predict the adverse reactions to irinotecan chemotherapy than detection of UGT1A1＊28 or UGT1A1＊6 genotype.

关 键 词：UGT1A1 基因多态性 伊立替康 不良反应 

分 类 号：R730.53[医药卫生—肿瘤]