UGT1A1基因多肽性与伊立替康联合雷替曲塞治疗晚期结直肠癌的临床分析

Clinical Analysis of UGT1A1 Gene Polypeptide and Irinotecan and Reticuthet in the Treatment of Advanced Colorectal Cancer

目的研究尿苷二磷酸葡糖苷酸转移酶1A1(UGT1A1)基因多态性与伊立替康联合雷替曲塞化疗方案治疗晚期结直肠癌的疗效及不良反应相关性。方法方便选取2016年5月—2017年10月于江苏大学附属武进人民医院肿瘤内科接受伊立替康联合雷替曲塞治疗的晚期结直肠癌患者60例,提取外周血中基因组DNA,PCR法扩增UGT1A1*6和UGT1A1*28基因的相应片段,双向测序法分析PCR产物,检测患者UGT1A1*6和UGT1A1*28基因型,分析UGT1A1基因多态性情况,并对给予伊立替康联合雷替曲塞化疗方案治疗的结直肠癌患者进行随访,记录疗效以及不良反应情况。结果 60例结直肠癌患者化疗后完全缓解(CR)0例,部分缓解(PR)11例,稳定(SD)22例,进展(PD)27例,有效率(RR)为18.3%;中位疾病进展时间(TTP)为7.8个月;中位生存期为13.5个月。疗程中出现的主要不良反应包括中性粒细胞减少、迟发性腹泻、转氨酶异常、血小板减少、疲劳及食欲下降等,分别占51.7%、20.0%、8.3%、11.7%、63.3%,多为I^II级;但UGT1A1*28基因型(TA6/7和TA7/7)显著增加发生III级以上中性粒细胞减少的风险(P<0.001),并增加整体不良反应发生率(P<0.05)。结论伊立替康联合雷替曲塞是治疗晚期结直肠癌有效方案,UGT1A1*28位点可预测伊立替康引起的不良反应,便于个体化治疗。

Objective This paper tries to study the correlation between the polymorphism of uridine two phosphate glucuronosyltransferase 1A1(UGT1A1)gene and irinotecan combined with reetrexed chemotherapy in the treatment of advanced colorectal cancer.Methods 60 cases of colorectal cancer patients from May 2016 to October 2017 in this hospital received irinotecan combined with pemetrexed for the treatment of thunder advanced colon were convenient selected and were extracted from peripheral blood genomic DNA,amplification of the corresponding fragment UGT1A1*6 and UGT1A1*28 gene PCR analysis method,PCR products sequencing method,the detection of patients with UGT1A1*6 and UGT1A1*28 gene type analysis of UGT1A1 gene polymorphism,and given irinotecan plus raltitrexed chemotherapy in the treatment of patients with colorectal cancer were followed up to record the efficacy and adverse reactions.Results 60 cases of colorectal cancer patients after chemotherapy,complete remission(CR)in 0 cases,partial remission(PR)in 11 cases,stable(SD)in 22 cases,progress(PD)in 27 cases,the effective rate(RR)was 18.3%,the median time to progression(TTP)was 7.8 months,and the median survival time was 13.5 months.The main adverse reactions appeared in the course of treatment included neutropenia and delayed diarrhea,abnormal transaminase,thrombocytopenia,fatigue and loss of appetite,accounted for 51.7%,20%,8.3%,11.7%,63.3%,more than I-II degree;but UGT1A1*28 genotype(TA6/7 and TA7/7)significantly increased risk of III the above neutropenia(P<0.001),and increase the overall incidence of adverse reactions(P<0.05).Conclusion Irinotecan combined with reetrexed is an effective treatment for advanced colorectal cancer.UGT1A1*28 site can predict irinotecan induced adverse reactions and facilitate individualized treatment.