作　　者： (白羽）; (吴海伟）; (刘颖）; (马旭）; (张艳华）;

机构地区： 北京大学肿瘤医院、暨北京市肿瘤防治研究所药剂科、恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处： 《中国临床药理学杂志》 2017年第17期1637-1640,共4页

摘　　要： 目的分析结直肠癌患者二氢嘧啶脱氢酶(DPYD)和亚甲基四氢叶酸还原酶(MTHFR)基因多态性的分布情况及基因多态性与卡培他滨方案治疗的药物不良反应的相关性。方法回顾性分析我院2015年4月至2016年10月治疗的81例结直肠癌患者DPYD、MTHFR基因型的分布情况,用数字荧光分子杂交(DFMH)技术对患者基因型进行测定。药物不良反应评价按照美国国立癌症研究所常规药物不良反应判定标准3.0(NCI-CTCAE3.0)实施。结果 81例结直肠癌患者DPYD基因检测未发现突变型,而MTHFR基因检测结果分布如下:MTHFR(1298A>C)野生型A/A、杂合突变型A/C和纯合突变型C/C分别为57例(70.37%),21例(25.93%)和3例(3.70%)。MTHFR基因纯合突变型(C/C型)和杂合突变型(A/C型)发生Ⅱ~Ⅳ度恶心呕吐风险高于野生型(A/A),分别为33.33%,19.05%和1.75%(P<0.05)。MTHFR突变型基因发生Ⅱ~Ⅳ度白细胞减少和血小板减少的风险高于野生型,但差异无统计学意义(P>0.05)。结论在我院尚未发现DPYD基因突变型患者,MTHFR基因多态性可以预测卡培他滨方案治疗结直肠癌患者发生药物不良反应的风险。 Objective To analyze the distribution of dihydropyrimidine dehydrogenase （ DPYD ） and methylenetetrahydrofolate reductase （MTHFR） gene polymorphisms of eapeeitabine - based regimen, and to discuss the correlations of gene polymorphisms and toxicity in colorectal cancer patients. Methods Retrospective the cancer patients from April 2015 to October 2016, who had received capecitabine - based regimen chemotherapy were included in this study. The DPYD and MTHFR genotype of 81 patients were analyzed by digital fluorescence molecular hybridization （DFMH）. The adverse reactions were evaluated according to tile National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 （NCI - CTCAE）. Results A total of 81 colorectal cancer patients with DPYD and MTHFR genotype were analyzed. Furthermore, we do not discover the mutation of DPYD genotype in our hospital. The distribution of MTHFR genotypes were as follows ： MTHFR （1298A 〉 C） wild genotype A/A of 70. 37% （57/81 cases）, heterozygousmutant genotype AZC of 25.93% （21/81 cases）, and homozygous mutant genotype C/C of 3.73% （3/81 cases）. The risk of nausea and vomiting （ from grade Ⅱ to grade Ⅳ ） in patients carrying A/C （ 19.05% ） and C/C （ 33.33% ） were higher than that in wild type （ 1.75 % , P 〈 O. 05 ）. We also found that mutant genotype of MTHFR increase the risk of leukopenia and thrombocytopenia （ from grade 11 ＇to grade 1V ）, the difference was not significant （P 〉 0. 05 ）. Conclusion There is no DPYD gene mutation in our study. Besides, MTHFR gene polymorphisms could predict eapecitabine -related adverse reactions in cancer patients.

关 键 词： 二氢嘧啶脱氢酶 亚甲基四氢叶酸还原酶 基因多态性 卡培他滨 药物不良反应