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目的探讨舟山群岛结直肠癌患者中尿苷二磷酸葡糖醛酸转移酶1A1(UGT1A1)基因多态性与伊立替康(CPT-11)疗效和不良反应之间的相关性。方法以CPT-11为主的FOLFIRI方案治疗并随访,同时抽提外周血基因组DNA测定UGT1A1启动子区28(UUGT1A1*28)的基因型,分析UGT1A1基因多态性及其与化疗毒性、疗效和预后之间的相关性。结果在78例使用CPT-11治疗的结直肠癌患者中,UGT1A1*28野生型TA(6/6)有58例,占74.4%;杂合突变型TA(6/7)有16例,占20.5%;纯合突变型TA(7/7)有4例,占5.1%。UGT1A1*28非野生型(6/7+7/7)患者发生腹泻的概率明显高于野生型患者(χ~2=18.347,P=0.000),而呕吐、中性粒细胞减少,以及疗效和存活状态与UGT1A1*28基因多态性无关。UGT1A1*28非野生型患者(6/7+7/7)随着用药次数增加,腹泻(F=8.506,P=0.009)和中性粒细胞减少(F=5.262,P=0.034)等不良反应的发生率明显增大。UGT1A1*28基因多态性不是独立的预后因素。结论舟山群岛UGT1A1*28基因突变情况符合亚洲人的特征,以CPT-11为主的FOLFIRI方案治疗结直肠癌的疗效值得肯定,但需注意根据UGT1A1的基因型进行剂量调整。
Objective To investigate the association between UGT1A1 gene polymorphism and the efficacy and adverse reactions of irinotecan (CPT-11) in patients with colorectal cancer of Zhoushan Archipelago. Methods The genotypes of UGT1A1 promoter region 28 (UUGT1A1 * 28) were genotyped by the CPT-11-based FOLFIRI regimen. Genotypes of UGT1A1 promoter region 28 (UUGT1A1 * 28) were extracted from the peripheral blood samples. The UGT1A1 gene polymorphism and its association with chemotherapy toxicity, The correlation between the prognosis. Results Among the 78 patients with colorectal cancer treated with CPT-11, there were 58 cases of UGT1A1 * 28 wild type TA (6/6), accounting for 74.4%. There were 16 cases of heterozygous mutant TA (6/7) 20.5%; homozygous mutant TA (7/7) in 4 cases, accounting for 5.1%. The incidence of diarrhea in UGT1A1 * 28 non-wild type (6/7 + 7/7) patients was significantly higher than that in wild type patients (χ ~ 2 = 18.347, P = 0.000), while vomiting, neutropenia, Survival status has nothing to do with UGT1A1 * 28 gene polymorphism. There was no adverse reaction such as diarrhea (F = 8.506, P = 0.009) and neutropenia (F = 5.262, P = 0.034) with the increase of treatment times in UGT1A1 * 28 non-wild type patients (6/7 + The incidence increased significantly. UGT1A1 * 28 gene polymorphism is not an independent prognostic factor. Conclusion The mutation of UGT1A1 * 28 gene in Zhoushan Archipelago is in accordance with the characteristics of Asians. The efficacy of CPF-11-based FOLFIRI regimen in the treatment of colorectal cancer is worthy of attention. However, the dosage of UGT1A1 should be adjusted according to the genotype of UGT1A1.