UGT1A1基因多态性与胃癌伊立替康化疗疗效和毒性的关系

Correlation of UGT1A1 Gene Polymorphism with the Efficacy and Toxicity of Irinotecan for Chem-otherapy of Gastric Cancer

[目的]探讨尿苷二磷酸葡糖醛酸转移酶1A1（UGT1A1）基因多态性与胃癌伊立替康化疗疗效和毒性的关系。[方法]67例胃癌患者治疗前采集外周抗凝静脉血进行DNA提取，采用聚合酶链式反应（PCR）进行扩增，测序；评价伊立替康治疗的毒性及疗效，分析UGT1A1基因多态性与胃癌伊立替康化疗疗效和毒性的关系。[结果]（TA）6/（TA）6野生基因型、（TA）6/（TA）7杂合基因型及（TA）7/（TA）7纯合突变型的患病率分别为80．6％（54/67）、14．9％（10/67）、4．5％（3/67）；UGT1A1＊28非野生型的基因多态性患者发生Ⅲ级以上腹泻38．5％显著高于野生基因型11．1％（ P ＜0．05）；UGT1A1＊28非野生型基因患者需下调伊立替康剂量的患者多于野生基因型（46．2％ vs18．5％，P＜0．05）；野生基因型与非野生基因型组疗效比较无统计学差异（ P＞0．05）。[结论]伊立替康治疗的胃癌患者中，UGT1A1＊28非野生型的基因多态性患者发生重度腹泻风险较高，基因多态性对疗效无明显影响。

[Objective] To explore the correlation of uridine diphosphate glucuronyl transferase 1A1（UGT1A1） gene polymorphism with the efficacy and toxicity of irinotecan for chemotherapy of gastric cancer .[Methods]Peripheral antico-agulation venous blood was collected from 67 patients with gastric cancer before DNA extraction .Polymerase chain reac-tion（PCR） was used for amplifying and sequencing .Toxicity and efficacy of irinotecan were evaluated .The correlation of UGT1A1 gene polymorphism with the efficacy and toxicity of irinotecan for chemotherapy of gastric cancer was analyzed .[Results] The prevalence of （TA ）6/（TA ）6 wild genotype ,（TA ）6/（TA ）7 heterozygous genotype and （TA ）7/（TA ）7 ho-mozygous mutant type was 80 .6% （54/67） ,14 .9% （10/67） and 4 .5% （3/67） ,respectively .The incidence of over Ⅲdegree diarrhea in patients with UGT 1A1＊28 non-wild-type gene polymorphism was 38 .5% which was markedly higher than that of patients with UGT 1A1＊28 wild-type gene polymorphism（11 .1% ）（ P〈0 .05） .The number of patients with UGT1A1＊28 non-wild-type gene who should reduce the dose of irinotecan was higher than that of patients with UGT1A1＊28 wild-type gene（46 .2% vs 18 .5% ,P〈0 .05） .There was no significant difference in the efficacy between wild genotype and non-wild genotype（ P〉0 .05） .[Conclusion]Patients with UGT1A1＊28 non-wild-type gene polymor-phism during irinotecan for the treatment of patients with gastric cancer have high risk of severe diarrhea .Gene polymor-phism has no obvious effect on the efficacy .