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中国临床药理学与治疗学 ›› 2022, Vol. 27 ›› Issue (2): 171-177.doi: 10.12092/j.issn.1009-2501.2022.02.007

• 临床药理学 • 上一篇    下一篇

有机阳离子转运体基因多态性与奥沙利铂毒性及疗效的相关性研究

陈佳音1,王丽1,王立军1,童刚领1,马洁1,陈西敬2,卢杨2   

  1. 1北京大学深圳医院,深圳 518036,广东;2中国药科大学基础医学与临床药学学院临床药物代谢动力学研究室,南京 211198,江苏

  • 收稿日期:2022-01-11 修回日期:2022-02-07 出版日期:2022-02-26 发布日期:2022-03-09
  • 通讯作者: 卢杨,男,特聘副研究员,硕士生导师,研究方向:药物代谢动力学。 Tel: 025-86185379 E-mail: luyangcpu@hotmail.com
  • 作者简介:陈佳音,女,博士,副主任药师,研究方向:临床药学。 E-mail: 13269288@qq.com
  • 基金资助:
    广东省科技创新战略专项资金(基础与应用基础研究方向,2018A0303100026);江苏省研究型医院学会精益化用药-石药专项科研基金(JY202040)

Correlation between organic cation transporter gene polymorphisms and the toxicities and clinical response of oxaliplatin

CHEN Jiayin1, WANG Li1, WANG Lijun1, TONG Gangling1, MA Jie1, CHEN Xijing2, LU Yang2   

  1. 1Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China; 2Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China
  • Received:2022-01-11 Revised:2022-02-07 Online:2022-02-26 Published:2022-03-09

摘要: 目的:探讨有机阳离子转运体1的编码基因SLC22A1的SNP位点rs628031、rs650284、rs683369基因多态性与奥沙利铂毒性及临床疗效之间的相关性。方法:选取2018年1月至6月在北京大学深圳医院肿瘤科住院的72例结直肠癌患者,收集患者外周静脉血并提取DNA样本,利用SNaPshot SNP分型技术确定研究位点的基因型并分析。根据常见不良事件评价标准(CTCAE5.0版)评估奥沙利铂的胃肠道毒性、血液毒性以及神经毒性;根据实体瘤的疗效评价标准(RECIST 1.1)评估患者的化疗疗效,结合患者其他临床资料进行统计分析。结果:卡方检验结果显示SLC22A1基因位点rs628031和rs683369的多态性可能与奥沙利铂的化疗毒性及疗效相关。与rs628031 GG基因型相比,携带GA或AA基因型的患者3级恶心呕吐发生率更低(P=0.017),同时疗效反应性也可能更差(P=0.008);与rs683369 CC基因型相比,携带GC或GG基因型的患者3级恶心呕吐发生率更低(P=0.002),同时疗效反应性也可能更差(P=0.014)。结论:SLC22A1的基因多态性与奥沙利铂的毒性及疗效之间存在相关性,可能为接受奥沙利铂治疗的结直肠癌患者的个体化方案调整及预后判断带来帮助。

关键词: SLC22A1基因, 有机阳离子转运体, 基因多态性, 奥沙利铂

Abstract: AIM: To investigate the relationship between genotypes of rs628031, rs650284, rs683369 of SLC22A1 gene and the toxicities and clinical response of oxaliplatin in patients with colorectal cancer.  METHODS: A total of 72 patients diagnosed as colorectal cancer during January 2018 to June 2018 were selected and all patients received oxaliplatin treatment. Their peripheral venous blood was collected and genotyping was conducted by using SNaPshot. The toxicities including gastrointestinal toxicity, hematological toxicity and peripheral neurotoxicity were evaluated according to the Common Terminology Criteria Adverse Events (CTCAE) Version 5.0. Clinical response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1). RESULTS: The results of Chi-test showed that different genotypes of SLC22A1 SNP sites rs628031 and rs683369 may be related to the toxicities and clinical response of oxaliplatin significantly. Specifically, when compared with the patients with GG type of rs628031, the patients with the GA or AA type had a lower incidence of grade 3 nausea and vomiting (P=0.017) and may also be less responsive to efficacy (P=0.008). When compared with the patients with CC type of rs683369, the patients with the GC or GG type had a lower incidence of grade 3 nausea and vomiting (P=0.002) and may also be less responsive to efficacy (P=0.014).CONCLUSION: The polymorphisms of SLC22A1 gene are closely related to the toxicities and clinical response of oxaliplatin in patients with colorectal cancer, which may be helpful for improving clinical treatment.

Key words: SLC22A1 gene, organic cation transporters, polymorphisms, oxaliplatin

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