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目的评价伊立替康(CVT-11)联合5-氟尿嘧啶(5-Fu)和亚叶酸钙(LV)治疗晚期大肠癌的毒性与尿苷二磷酸葡糖苷酸转移酶1A(UGT1A)基因多态性的相关性。方法收集70例晚期大肠癌患者及健康志愿者的外周血,提取基因组DNA,PCR法扩增目的基因片段,直接测序法分析UGT1A基因多态性,并与毒性进行相关性分析。结果70例晚期大肠癌患者的3～4度中性粒细胞减少发生率为20.O%(14/70);2～4度迟发性腹泻发生率为22.9%(16/70),其中3-4度迟发性腹泻率仅为5.7%(4/70)。UGT1A1*28的野生基因型TA6/6患者的2-4度迟发性腹泻发生率为15.7%,低于TA6/7和TA7/7基因型的患者(P=0.027)。健康人群和大肠癌患者UGT1A基因家族中各个基因多态性的分布无差别。结论UGT1A1*28的野生基因型TA6/6在中国人中分布频率较高,这也是CPT-11为主方案治疗晚期大肠癌发生严重迟发性腹泻较少的原因。
Objective To evaluate the relationship between the toxicity of irinotecan (CVT-11) combined with 5-fluorouracil and leucovorin (LV) in the treatment of advanced colorectal cancer and the polymorphism of uridine diphosphate glucuronosyltransferase 1A (UGT1A) Relevance. Methods The peripheral blood of 70 patients with advanced colorectal cancer and healthy volunteers were collected and genomic DNA was extracted. The target gene fragment was amplified by PCR and the UGT1A gene polymorphism was analyzed by direct sequencing. The correlation was analyzed with the toxicity. Results The incidence of 3- to 4-degree neutropenia was 70.0% (14/70) in 70 patients with advanced colorectal cancer and 22.9% (16/70) in 2-4 patients with delayed diarrhea Delayed diarrhea rates of 3-4 degrees were only 5.7% (4/70). The incidence of 2-4 degrees delayed diarrhea in wild-type TA6 / 6 patients with UGT1A1 * 28 was 15.7%, lower than those in TA6 / 7 and TA7 / 7 genotypes (P = 0.027). There was no difference in the distribution of each gene polymorphism in the UGT1A gene family between healthy people and colorectal cancer patients. Conclusion The wild type TA6 / 6 of UGT1A1 * 28 is highly distributed in Chinese population, which is also the reason why CPT-11 is the main regimen for the treatment of late-stage colorectal cancer with severe delayed diarrhea.