The Tailor Made Therapy of Anti-Cancer Drugs

抗癌药物的量身定制疗法

基本信息

批准号：
18590516
负责人：
KOBAYASHI Shinichi
金额：
$ 2.53万
依托单位：
St.Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590516/
关键词：
Tailor made therapy Anti-cancer drugs Gene polymorphism Drug metabolizing enzymes Transporter DPD Haplotype

项目摘要

Anti-cancer drugs have a many serious side effects is well known. There are possible that the gene polymorphisms of drug metabolizing enzymes and drug transporter are affects on the anti-cancer drugs pharmacokinetics, pharmacodynamics and side effects. Further ethnic differences of gene polymorphisms of the several drug metabolizing enzymes and transporter have been reported. Therefore, we investigated that the gene polymorphisms of drug metabolizing enzymes and drug transporter, which are closely related anti-cancer drugs in the Japanese population. Genomic DNA obtained from the non cancer liver tissues by surgical resection for liver disease. Written informed consent was obtained from 34 patients with liver disease. This study was approved by the ethics committee of St. Marianna University School of Medicine. We can identified gene polymorphisms of CYP's (CYP1A2*1F, CYP2C19*2, *3, CYP2D6*4, *5, *6, *10, CYP3A4*4, *16) and MDR1 (-41A/G, -129T/C, 1236T/C, 2677G/A, T, 3435C/T, 4036A/G). The allele frequencies of CYP's were (CYP1A2*1F(69.4%), CYP2C19*2, *3(41.7%), CYP2D6*4, *5, *6, *10(42.6%), CYP3A4*4, *16(2.9%)), and MDR1 were (-41A/G(16.7%), -129T/C(9.4%), 1236T/C(24.2%), 2677G/A, T(64.6%), 3435C/T(40.9%), 4036A/G(27.3%)), respectively. The allele frequencies of CYP1A2, CYP2C19, CYP2D6, and 12677G/A, T, and 3435C/Tof MDR-1 were shown to be high compared to previously reports. These result indicated that the needs for attention on the using drugs for metabolism by these CYP's and for transport by MDR-1. These data suggested that the pharmacogenomic data is available on the tailor made therapeutic strategy of patients having above gene polymorphisms in Japanese.

抗癌药物有许多严重的副作用是众所周知的。药物代谢酶和药物转运蛋白的基因多态性可能影响抗癌药物的药代动力学、药效学和副作用。据报道，几种药物代谢酶和转运蛋白的基因多态性存在进一步的种族差异。因此，我们研究了日本人群中与抗癌药物密切相关的药物代谢酶和药物转运蛋白的基因多态性。通过肝病手术切除从非癌肝组织中获得基因组 DNA。 34 名肝病患者获得了书面知情同意书。这项研究得到了圣玛丽安娜大学医学院伦理委员会的批准。我们可以鉴定 CYP 的基因多态性（CYP1A2*1F、CYP2C19*2、*3、CYP2D6*4、*5、*6、*10、CYP3A4*4、*16）和 MDR1（-41A/G、-129T/） C、1236T/C、2677G/A、T、 3435C/T、4036A/G）。 CYP的等位基因频率为(CYP1A2*1F(69.4%)、CYP2C19*2、*3(41.7%)、CYP2D6*4、*5、*6、*10(42.6%)、CYP3A4*4、*16( 2.9%))，MDR1 为 (-41A/G(16.7%)，分别为-129T/C(9.4%)、1236T/C(24.2%)、2677G/A、T(64.6%)、3435C/T(40.9%)、4036A/G(27.3%))。与之前的报道相比，CYP1A2、CYP2C19、CYP2D6 和 12677G/A、T 和 3435C/Tof MDR-1 的等位基因频率较高。这些结果表明，在使用药物时需要注意这些CYP的代谢和MDR-1的转运。这些数据表明，药物基因组学数据可用于为具有上述基因多态性的日本患者量身定制治疗策略。