UGT1A1基因多态性与伊立替康临床用药安全性及疗效的关系

Relationship between UGT1A1 gene polymorphism and clinical safety and efficacy of irinotecan

目的:研究UGT1A1基因多态性与伊立替康治疗结直肠癌患者的不良反应及疗效之间的关系。方法:自外周血中抽提基因组DNA,进行PCR扩增,应用直接测序法分析2012年3月至2013年3月,于我院行基因检测的65例结直肠癌患者UGT1A1*28和UGT1A1*6基因多态性的分布情况。并对这65例应用含伊立替康方案化疗的患者出现的不良反应及化疗疗效,进行观察记录,比较不同基因型间的差异。结果:65例患者中,UGT1A1*28野生型TA6/6有49例(75.4%),杂合突变型TA6/7有14例(21.5%),纯合突变型TA7/7有2例(3.1%)。UGT1A1*6野生型G/G有47例(72.3%),杂合突变型G/A有15例(23.1%),纯合突变型A/A有3例(4.6%)。在以上65例结直肠癌患者中,UGT1A1基因启动子区28位点,TA6/6、TA6/7和TA7/7型,发生3级以上腹泻者分别为8.2%、37.5%;发生3级以上中性粒细胞减少者分别为28.6%、62.5%。UGT1A1基因启动子区6位点,G/G、G/A和A/A型,发生3级以上腹泻者分别为12.8%、44.4%;发生3级以上中性粒细胞减少者分别为14.9%、22.2%。各组之间疗效无统计学差异。结论:患者UGT1A1*28和UGT1A1*6多态性分布基本一致,UGT1A1*28突变型可以使应用含伊立替康化疗患者发生3级以上腹泻和中性粒细胞减少的风险增加。UGT1A1*6突变型可增加3级以上腹泻的发生风险。因此,UGT1A1基因型的检测对伊立替康相关的不良反应有一定的预测作用,可提高用药安全性,在临床用药中起到了指导作用。

Objective：To study the relationship between UGT1A1 gene polymorphisms and toxicity and efficacy in patients with colorectal cancer treated with irinotecan.Methods：From the peripheral blood genomic DNA was extracted,amplified by PCR,analyzed by direct sequencing,the gene detection in our hospital 65 patients with colorectal cancer about UGT1A1＊ 28 gene and UGT1A1＊ 6 gene polymorphism distribution.And the adverse reactions and the efficacy of chemotherapy in 65 patients with the application of irinotecan chemotherapy were observed and recorded,the difference among different genotypes.Results：In 65 patients,wild type TA6 /6 of UGT1A1 ＊ 28 had 49 cases（ 75.4%）,heterozygous mutation of TA6 /7 in 14 cases（ 21.5%）,homozygous mutation genotype of TA7/7 in 2 cases（3.1%）.Wild type G/G of UGT1A1＊ 6 had 47 cases（ 72.3%）,heterozygous mutation of G/A in 15 cases（ 23.1%）,homozygous mutation genotype of A / A in 3 cases（ 4.6%）.In 65 cases of colorectal cancer,UGT1A1 gene promoter region was in 28 loci,TA6 /6,TA6 /7 and TA7 /7,more than 3 grade diarrhea were 8.2%,37.5%.More than 3 grade neutropenia were 28.6%,62.5%.There was no significant difference in the efficacy of each group.Conclusion：Consistent with UGT1A1＊ 28 and the distribution of UGT1A1 ＊ 6 polymorphism,the UGT1A1 ＊ 28 mutant can be used with irinotecan chemotherapy in patients with risk of grade 3 diarrhea and neutropenia increases.UGT1A1 ＊ 6 mutation may increase the risk of developing grade 3 diarrhea.Therefore,the detection of UGT1A1 genotypes is a predictor of adverse reactions of irinotecan related,which may improve the drug safety in clinical medication,play a guiding role.