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目的探讨尿苷二磷酸葡萄醛酸转移酶1A1(UGT1A1)基因多态性对伊立替康治疗晚期结直肠癌患者疗效及不良反应的影响。方法选取2015年2月至2016年12月间新疆维吾尔自治区人民医院收治的62例晚期结直肠癌患者,所有患者均采用伊立替康、亚叶酸钙和氟尿嘧啶(FOLFIRI方案)进行治疗。采用聚合酶链反应(PCR)技术扩增UGT1A1*28、UGT1A1*6基因片段,分析基因型与不良反应及化疗疗效的关系。结果不同年龄、性别、转移数目、癌症类型和分化程度患者不良反应的比较,差异无统计学意义(P>0.05)。UGT1A1*28基因非野生型患者3~4度腹泻比例为38.1%,明显高于野生型患者,差异有统计学意义(P<0.05)。UGT1A1*6基因非野生型患者3~4度中性粒细胞减少比例为77.8%,明显高于野生型患者,差异有统计学意义(P<0.05);双野生型(DW)、单个位点变异型(SV)和双个位点变异型(DV)不良反应的比较,差异无统计学意义(P>0.05);62例患者客观缓解率为40.3%,UGT1A1基因多态性与化疗疗效无明显相关性,差异无统计学意义(P>0.05)。结论 UGT1A1基因型多态性与伊立替康治疗晚期结直肠癌患者不良反应有一定关系,而与化疗疗效无关。
Objective To investigate the effect of uridine diphosphate glucuronyl transferase 1A1 (UGT1A1) gene polymorphism on the efficacy and adverse reactions of irinotecan in patients with advanced colorectal cancer. Methods Sixty-two patients with advanced colorectal cancer who were admitted to People’s Hospital of Xinjiang Uyghur Autonomous Region from February 2015 to December 2016 were selected. All patients were treated with irinotecan, leucovorin and fluorouracil (FOLFIRI regimen). The UGT1A1 * 28 and UGT1A1 * 6 gene fragments were amplified by polymerase chain reaction (PCR), and the relationship between genotype and adverse reaction and chemotherapy efficacy was analyzed. Results There were no significant differences in adverse reactions between patients of different ages, gender, number of metastases, type of cancer and degree of differentiation (P> 0.05). The proportion of 3-4 degree diarrhea in UGT1A1 * 28 gene non-wild type was 38.1%, which was significantly higher than that in wild type (P <0.05). The 3 to 4 degree neutropenia ratio in non-wild type patients with UGT1A1 * 6 gene was 77.8%, which was significantly higher than that in wild type patients (P <0.05). Double wild type (DW) There was no significant difference between the two groups (P> 0.05). The objective response rate of 62 patients was 40.3%. The UGT1A1 gene polymorphism was not related to the chemotherapy efficacy Significant correlation, the difference was not statistically significant (P> 0.05). Conclusion The polymorphism of UGT1A1 genotype is related to the adverse reaction of irinotecan in patients with advanced colorectal cancer, but not with chemotherapy.