UGT1A*28基因多态性对伊立替康治疗晚期结直肠癌疗效及不良反应的影响——华南地区研究报告

The influence of UGT1A*28 gene polymorphism onefficacy and adverse effect of combined irinotecan chemotherapy for late-staged colorectal cancer, a preliminary report in southern China

目的检测华南地区伊立替康联合方案治疗晚期结直肠癌患者UGT1A*28基因的多态性,观察伊立替康治疗晚期结直肠癌的疗效和不良反应,用于指导临床用药。方法 收集华南地区晚期结直肠癌患者共214例,给予伊立替康联合5-FU/LV方案化疗,并进行UGT1A1*28基因多态性测定,观察患者疗效和不良反应。结果 167例(80.29%)患者为TA6/6纯合野生基因型,40例(19.23%)患者为TA6/7杂合突变基因型,1例(0.48%)患者为TA7/7纯合突变基因型。TA6/6野生基因型和突变基因型患者的客观有效率(ORR)分别为31.20%和20.0%(P=0.191),疾病控制率(DCR)分别为90.78%和74.29%(P=0.008)。TA6/7及TA7/7突变基因型患者采用伊立替康治疗时严重延迟性腹泻和粒细胞减少症发生率分别为9.76%、9.76%,高于TA6/6野生基因型的5.39%和3.59%。结论 UGT1A1*28不同基因型对伊立替康治疗晚期结直肠癌的疗效和不良反应均有差异。

Objective To detect the polymorphism of UGT1A1*28 in late-staged colorectal cancer patients in southern China, and observe the efficacy and adverse effect of combined irinotecan chemotherapy for late-staged colorectal cancer. Methods A total of 214 patients with late-staged colorectal cancer in southern China were enrolled, and received irinotecan plus 5-FU / LV chemotherapy. UGT1A*28 gene polymorphismwas determined and the efficacy and adverse effect were observed, the relationship between them was analyzed. Results TA6 / 6 wild genotype was found in 167 cases(80.29%), TA6 / 7 heterozygous mutation genotype in 40 cases(19.23%), TA7 / 7 pure mutation genotype in one case(0.48%). The overall response rates(ORR) of TA6 / 6 wild genotype and mutation genotype groups were 31.20% and 20.0%(P =0.191), the disease control rates(DCR) were 90.78% and 74.29% respectively(P=0.008). Compared with TA6 / 6 group, TA6 / 7 and TA7 / 7mutation genotype groups had higher incidences of serious delayed diarrhea(9.76% vs. 5.39%) and granulocytopenia(9.76% vs. 3.59%). Conclusion There were differences in efficacy and adverse effect of combined irinotecan chemotherapy for late-staged colorectal cancer patients among different types of UGT1A1*28.