权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

THE ROLE OF GENETIC POLYMORPHISMS OF DRUG TRANSPORTER GENES FOR THE TREATMENT OF LUNG CANCER

药物转运基因的遗传多态性在肺癌治疗中的作用

基本信息

批准号：
17590786
负责人：
HASEGAWA Yoshinori
金额：
$ 2.24万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590786/
关键词：
Irinotecan ABC transporters gene polymorphisms ABCC2 OATP-C UGT1A1^*28 UGT1A1*28 ABCG2

项目摘要

Irinotecan unexpectedly causes severe, occasionally fatal, toxicity of leukopenia or diarrhea. Adenosine triphosphate-binding cassette transporters (ABCC2) transport irinotecan and its metabolites from hepatocytes to the bile. We assessed whether variant forms of ABCC2 would affect inter-patient variations in sensitivity to irinotecan toxicity in 120 Japanese patients with a cancer. The genotyping of ABCC2 was performed by direct sequencing of the PCR fragment. We found five polymorphisms in ABCC2. ABCC2 2375A>G is a new polymorphism, substituting aspartic acid for glycine. Univariate logistic regression analysis found no significant association between severe toxicities and carrying at ABCC2 polymorphisms. The results suggested that the determination of nucleic polymorphisms of ABCC2 would not be useful for predicting severe toxicities by irinotecan. On the other hand, organic anion transporting polypeptide C (OATP-C) plays a major role in the transport of SN-38 from portal venous blood to hepartocytes. The allele frequencies of OATP-C^*1 a, OATP-C^*1b, and OATP-C^*15 were 0.31, 0.58, and 0.11, respectively. Logistic regression analysis did not show any significant association between the occurrence of severe toxicity and carrying OATP-C^*15. The double variants for OATP-C^*15 and UGT1A1 ^*28 tended to be associated with the occurrence of severe toxicity, although it was not statistically significant.

伊立替康意外地引起严重的、有时致命的白细胞减少症或腹泻毒性。三磷酸腺苷结合盒转运蛋白 (ABCC2) 将伊立替康及其代谢物从肝细胞转运至胆汁。我们在 120 名日本癌症患者中评估了 ABCC2 的变异形式是否会影响患者对伊立替康毒性敏感性的差异。 ABCC2 的基因分型通过 PCR 片段的直接测序进行。我们在 ABCC2 中发现了 5 个多态性。 ABCC2 2375A>G 是一种新的多态性，用天冬氨酸取代甘氨酸。单变量逻辑回归分析发现严重毒性与携带 ABCC2 多态性之间没有显着关联。结果表明，ABCC2 核酸多态性的测定对于预测伊立替康的严重毒性无用。另一方面，有机阴离子转运多肽 C (OATP-C) 在 SN-38 从门静脉血转运至肝细胞的过程中起主要作用。 OATP-C^*1a、OATP-C^*1b和OATP-C^*15的等位基因频率分别为0.31、0.58和0.11。 Logistic回归分析未显示严重毒性的发生与携带OATP-C^*15之间存在任何显着关联。 OATP-C^*15 和 UGT1A1^*28 的双变异往往与严重毒性的发生相关，尽管没有统计学意义。