UGT1A1基因多态性与伊立替康治疗晚期胃肠道肿瘤不良反应和疗效的相关性分析

Correlation analysis between UGT1A1 gene polymorphism,and the toxicity and efficacy of irinotecan in the treatment of advanced gastrointestinal cancer

目的:探讨尿苷二磷酸葡糖苷酸转移酶1A1(UGT1A1)基因多态性与伊立替康治疗晚期胃肠道肿瘤不良反应和疗效的关系。方法:在62例含伊立替康方案化疗的晚期胃肠道肿瘤病人化疗前,使用PCR-HRM法获取研究对象的外周血并检测UGT1A1基因型,分析UGT1A1基因多态性与化疗不良反应、疗效的相关性。结果:UGT1A1*28位点野生型(TA6/6)、杂合突变型(TA6/7)、纯合突变型(TA7/7)分布频率分别是77.4%、11.3%、11.3%;UGT1A1*6位点野生型(G/G)占79.1%,杂合突变型(G/A)占16.1%,纯合突变型(A/A)占4.8%。UGT1A1*28和UGT1A1*6突变型均较其野生型增加了病人发生3级以上腹泻和中性粒细胞减少的风险(P<0.05~P<0.01)。UGT1A1各基因型之间的疗效差异均无统计学意义(P>0.05)。结论:在含伊立替康方案治疗的晚期胃肠道肿瘤中,UGT1A1*28和UGT1A1*6的突变可以作为伊立替康相关严重延迟性腹泻和中性粒细胞减少的预测指标。未发现UGT1A1基因多态性与疗效之间存在相关性。

Objective：To investigate the correlations between uridine-diphosphoglucuronate glucuronosyltransferase 1 family polypetide A1（UGT1A1） gene polymorphism,and the toxicity and efficacy of irinotecan in the treatment of advanced gastrointestinal cancer. Methods：The UGT1A1 genotypes in 62 advanced gastrointestinal cancer patients before treatment with irinotecan were detected using the polymerase chain reaction and high-resolution melting analysis. The correlations between UGT1A1 gene polymorphisms, and the toxicity and efficacy of irinotecan were analyzed. Results：The distribution frequency of wild-type（TA6/6）,heterozygous mutant-type （TA6/7） and homozygous mutant-type（TA7/7） in UGT1A1＊28 loci were 77. 4%,11. 3%,and 11. 3%,respectively. The proportion of wild-type（G/G）,heterozygous mutant-type（G/A） and homozygous mutant-type（A/A） in UGT1A1＊6 loci were 79. 1%,16. 1%and 4. 8%,respectively. Compared with the wild types of UGT1A1＊28 and UGT1A1＊6,the risks of the more than grade 3 diarrhea and neutropenia in mutant types of UGT1A1＊28 and UGT1A1＊6 increased（P〈0. 05 to P〈0. 01）. The difference of the efficacy between different genotypes of UGT1A1 was not statistically significant（P〉0. 05）. Conclusions：During the irinotecan in the treatment of advanced gastrointestinal cancer, the locus mutations of UGT1A1＊28 and UGT1A1＊6 can be regarded as the predictors of irinotecan-associated severe delayed diarrhea and neutropenia. The correlation between UGT1A1 gene polymorphism and efficacy of irinotecan is not found.