目的 探索我院肿瘤患者化疗药物相关单核苷酸多态性(SNPs)的分布特征,为临床药师开展以化疗药物相关SNPs为基础的肿瘤患者个体化用药指导提供参考。方法 采用荧光原位杂交技术通过荧光标记的特异性探针检测化疗药物相关SNPs,回顾性分析北京大学肿瘤医院2016年4月~2018年12月肿瘤患者的化疗相关SNPs的分布特征。采用SPSS24.0软件统计相关基因位点的等位基因和基因型的频率分布差异,分析基因分布是否符合Hardy-Weinberg平衡。参照国外不同人群的基因型频率数据,探讨中国肿瘤患者化疗药物相关SNPs的分布特征。结果 主要检测2 554例肿瘤患者6大类化疗药物17个化疗药物相关基因位点,其中CYP2D6(100C>T)、ABCB1(2677T>G)不符合Hardy-Weinberg平衡,其余15个基因位点均符合Hardy-Weinberg平衡。DPD、CYP2D6、UGT1A1的SNPs与国外人群存在较大差异,与国内报道基本相符。结论 中国肿瘤患者化疗药物相关SNPs分布有自身特点,临床药师应根据化疗药物相关SNPs提供个体化用药指导建议。基于药物基因组学的个体化用药,在参考PharmGKB等国际数据库的同时,国人的基因SNPs解读应结合国人的特点,不能完全参考国外人群数据库。
Abstract
OBJECTIVE To explore the distribution characteristics of chemotherapy drug-related single nucleotide polymorphisms(SNPs) in cancer patients in our hospital, and to provide the clinical reference for clinical pharmacists to guide the individualized therapy of cancer patients based on SNPs. METHODS Fluorescence-labelled specific probes were used to detect drug-related genes by fluorescence in situ hybridization. The drug-related SNPs of cancer patients from Apr 2016 to Dec 2018 in Peking University Cancer Hospital were retrospectively analyzed. SPSS24.0 software was used to statistically analyze the difference in the frequency distribution of alleles and genotypes, and the Hardy-Weinberg equilibrium test. The distribution characteristics of related gene loci in cancer patients in our hospital regarding the genotype frequency of different populations were studied. RESULTS A total of 17 chemotherapy drug-related gene loci were detected in 2 554 patients. CYP2D6(100C>T) and ABCB1(2677T>G) were not consistent with Hardy-Weinberg equilibrium, while the remaining 15 loci were in Hardy-Weinberg equilibrium. The allele frequencies of DPD, CYP2D6 and UGT1A1 of the Chinese population are significantly different from those of foreign population, which are consistent with internal reports. CONCLUSION The distribution of chemotherapy drug-related SNPs in Chinese tumor patients performs its characteristics. Clinical pharmacists should provide individualized medication advisements according to chemotherapy drug-related SNPs. Based on the application of pharmacogenomics, while referring to international databases such as PharmGKB, the interpretation of SNPs of the Chinese population should be combined with the characteristics of the Chinese population, and the database of the different population cannot be fully referenced.
关键词
药物基因组学 /
单核苷酸多态性 /
个体化用药 /
肿瘤
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Key words
pharmacogenomics /
single nucleotide polymorphism /
individualized medication /
cancer
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中图分类号：
R952
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