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目的:系统评价患者采用氟尿嘧啶类药物为基础化疗方案时出现3级以上的毒性反应与DPYD*2A、c.2846A>T和*13基因多态性的关系,期望为其个体化用药提供证据。方法:计算机检索EMbase、PubMed、The Cochrane Library、Clinical Trials、CNKI、CBM、万方和维普数据库,查找关于氟尿嘧啶类药物的毒性与DPYD*2A、c.2846A>T和*13基因多态性的关系的临床研究,检索时限均从建库截至2016年1月18日。对符合条件的研究,由2位研究者按照纳入和排除标准,独立筛选文献、提取资料、评价文献质量,并交叉核对后,采用RevMan 5.2和Stata 12.0软件进行Meta分析。结果:共纳入19篇文献,包括19个研究(n=9 133);结果显示,与野生型相比,DPYD*2A、c.2846A>T和*13三个位点的突变者服用氟尿嘧啶类药物发生3级以上毒性反应的风险明显较高(P<0.05)。结论:对于应用氟尿嘧啶类药物为基础化疗的肿瘤患者,建议用药前先检测DPYD*2A、c.2846A>T和*13基因型,若患者该基因发生突变,建议适当减少给药剂量或换用其他药物。
OBJECTIVE: To systematically evaluate the relationship between toxic reactions of grade 3 and DPYD * 2A, c.2846A> T and * 13 polymorphisms in patients receiving fluorouracil-based chemotherapy and to provide evidence for their individualized drug use. METHODS: We searched the EMbase, PubMed, The Cochrane Library, Clinical Trials, CNKI, CBM, Wanfang and VIP databases to find out the toxicities of fluorouracil drugs and DPYD * 2A, c.2846A> T and * 13 gene polymorphisms The relationship between clinical research, search time limit from the database as of January 18, 2016. For eligible studies, two researchers independently screened the literature, extracted data, evaluated the quality of the literature, and cross-checked the data according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.2 and Stata 12.0 software. RESULTS: A total of 19 articles were included, including 19 studies (n = 9,133). The results showed that compared with the wild type, the mutants of DPYD * 2A, c.2846A> T and * 13 took fluorouracil There was a significantly higher risk of drug toxicity above grade 3 (P <0.05). CONCLUSIONS: For patients with tumors based on fluorouracil chemotherapy, it is advisable to detect DPYD * 2A, c.2846A> T and * 13 genotypes before treatment. If the gene is mutated, it is advisable to reduce the dose or switch Other drugs.