The Tailor Made Therapy of Anti-Cancer Drugs

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体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。一些药物代谢酶和转运体基因多态性的进一步种族差异已被报道。因此，我们对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体的基因多态性进行了研究。通过肝脏疾病手术切除从非癌性肝组织中获得的基因组DNA。34例肝病患者获得书面知情同意。本研究经圣玛丽安娜大学医学院伦理委员会批准。我们发现了CYP的基因多态性（CYP1A2*1F、CYP2C19*2、*3、CYP2D6*4、*5、*6、*10、CYP3A4*4、*16）和MDR1的基因多态性（-41A/G、-129T/C、1236T/C、2677G/A、T、3435C/T、4036A/G）。CYP的等位基因频率(CYP1A2 * 1 f(69.4%)、CYP2C19 * 2 * 3(41.7%)、CYP2D6 * 4 * 5 * 6 * 10 (42.6%), CYP3A4 * 4 * 16(2.9%)),和凋亡(-41 A / G(16.7%)、-129 T / C(9.4%)、1236 T / C(24.2%)、2677 G / A、T(64.6%)、3435 C / T(40.9%)、4036 A / G(27.3%),分别为。与先前的报道相比，CYP1A2、CYP2C19、CYP2D6和MDR-1的12677G/A、T和3435C/T的等位基因频率较高。这些结果表明，需要重视这些CYP的代谢和MDR-1转运药物的使用。这些数据表明，药物基因组学数据可用于定制日本患者具有上述基因多态性的治疗策略。

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.