结直肠癌化疗后肝功能异常的影响因素分析

发布时间：2018-03-16 14:38

本文选题：结直肠癌　切入点：化疗后肝功能异常　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:肝脏是抗肿瘤药物主要的毒性靶器官之一。奥沙利铂、伊立替康和氟尿嘧啶这三种结直肠癌化疗的主要药物均有可预测的肝脏毒性。化疗在使结直肠癌患者获益的同时,其诱发的肝损伤也可能导致抗肿瘤治疗延迟而影响疗效,或者使患者错失治疗的最佳时期、延误其他治疗手段的实施。因此,研究结直肠癌化疗相关性肝损伤的临床特征和危险因素,对于减少和预防肝损伤,使化疗过程顺利实施,具有重要的意义。本研究探讨了结直肠癌化疗后肝功能异常的发生率、临床特征及其主要危险因素,并试图从遗传药理学角度研究药物代谢酶GSTs基因多态性与化疗后肝功能异常的相关性。方法:本研究按照纳入标准收集2014年1月至2016年12月山东大学齐鲁医院收治入院进行规范化疗的结直肠癌患者505例。在获得病人知情同意后,开展病例资料查阅和问卷调查,将其临床病例资料中可能对化疗后肝功能异常造成影响的因素分为患者因素、肝脏状况、原发病肿瘤特征、治疗因素四大类共20项进行详细记录;将化疗后出现肝功能异常的患者归入病例组,化疗后肝功能正常的患者归入对照组。采用单因素和多因素分析探讨上述因素与化疗后肝功能异常之间的关系。对同意接受药物代谢酶GSTs基因检测的患者收集其外周静脉血2毫升,检测GSTM1和GSTT1基因型,对GSTM1和GSTT1基因型与化疗后肝功能异常进行相关性分析。结果:1)本研究纳入的505例结直肠癌患者中,有279例发生化疗后肝功能异常,占55.25%;肝功能分级结果显示,1度肝损伤260例,2度肝损伤14例,3度肝损伤4例,4度肝损伤1例;达到肝损害标准的患者共69例,占]3.66%,对其肝损害类型进行划分,其中肝细胞损伤型56例,占到了绝大多数。2)单因素分析结果表明,与化疗后肝功能异常发生有统计学意义的相关因素为年龄、糖尿病病史、合并用药史、治疗类型、化疗药物、化疗方案、使用靶向药物;多因素分析结果表明,年龄60岁、糖尿病病史、合并用药史为化疗后肝功能异常发生的危险因素。3)GSTM1基因缺失型比例为46.43%,GSTT1基因缺失型比例为58.33%,GSTM1和GSTT1均为缺失型的比例为30.95%。相关性分析显示,GSTM1缺失型及GSTM1和GSTT1均为缺失型的患者发生化疗后肝功能异常的风险较高。结论:本研究中结直肠癌化疗后肝功能异常的发生率为55.25%,肝损害发生率为13.66%。结直肠癌化疗后肝功能异常的主要危险因素为年龄60岁、糖尿病病史、合并用药史。GSTM1缺失型及GSTM1和GSTT1均为缺失型的患者发生化疗后肝功能异常的风险较高。
[Abstract]:Objective: the liver is one of the main toxic target organs of antitumor drugs. Oxaliplatin, irinotecan and fluorouracil are the three main agents of chemotherapy for colorectal cancer, all of which have predictable hepatic toxicity. Chemotherapy benefits patients with colorectal cancer at the same time. The induced liver injury may also result in delayed anti-tumor therapy, or may cause patients to miss the best period of treatment and delay the implementation of other treatments. To study the clinical characteristics and risk factors of chemotherapy-associated liver injury in colorectal cancer is of great significance to reduce and prevent liver injury and make the chemotherapy process carry out smoothly. Clinical characteristics and main risk factors, The relationship between the polymorphism of drug metabolizing enzyme GSTs gene and liver dysfunction after chemotherapy was studied from the perspective of genetic pharmacology. Methods: according to the inclusive criteria, the study collected from Qilu Hospital, Shandong University from January 2014 to December 2016. 505 patients with colorectal cancer who were admitted to hospital for standardized chemotherapy. After obtaining the informed consent of the patient, The factors that may affect the liver function abnormality after chemotherapy are divided into patient factors, liver status, primary tumor characteristics, and so on. A total of 20 items were recorded in four categories of treatment factors, and the patients with abnormal liver function after chemotherapy were classified into the case group. The patients with normal liver function after chemotherapy were classified into the control group. The relationship between the above factors and liver dysfunction after chemotherapy was investigated by univariate and multivariate analysis. The patients who agreed to accept drug metabolizing enzyme GSTs gene were collected. Peripheral venous blood 2 ml, GSTM1 and GSTT1 genotypes were detected, and the correlation between GSTM1 and GSTT1 genotypes and liver dysfunction after chemotherapy was analyzed. Results among 505 patients with colorectal cancer, 279 had abnormal liver function after chemotherapy. The results of liver function grading showed that there were 260 cases of primary liver injury, 14 cases of grade 2 liver injury, 4 cases of liver injury of grade 3 and 1 case of liver injury of grade 4, and 69 cases (3.66%) of the patients who met the standard of liver damage were classified into the types of liver damage. The results of univariate analysis showed that age, history of diabetes, history of combined use of drugs, types of treatment, and chemotherapeutic drugs were significantly related to liver dysfunction after chemotherapy. Chemotherapy regimen, using targeted drugs; multivariate analysis showed that the age of 60 years, diabetes history, The proportion of GSTM1 gene deletion type was 46.43 and the proportion of GSTT1 gene deletion type was 58.33%. The proportion of GSTM1 and GSTT1 deletion type was 30.955.Relativity analysis showed that GSTM1 deletion type and GSTM1 and GSTT1 were deficient. Conclusion: in this study, the incidence of abnormal liver function after chemotherapy for colorectal cancer is 55.25, the incidence of liver damage is 13.66. The main risk of abnormal liver function after chemotherapy for colorectal cancer is 55.25. The risk factor is age 60, The risk of liver dysfunction after chemotherapy was higher in patients with diabetes history, GSTM1 deletion and GSTM1 and GSTT1 deletion.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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