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中华结直肠疾病电子杂志 ›› 2018, Vol. 07 ›› Issue (03) : 257 -261. doi: 10.3877/cma.j.issn.2095-3224.2018.03.012

所属专题: 文献

论著

药物转运体基因多态性对伊立替康治疗结直肠癌患者所致严重不良反应的影响
马超1, 金焰2, 段希斌1, 曹巍3, 邢国臣4, 易善永4, 李学民1,(), 王晓飞3,()   
  1. 1. 450007 郑州大学附属郑州中心医院肝胆胰外科
    2. 450007 郑州大学附属郑州中心医院乳腺和甲状腺外科
    3. 450007 郑州大学附属郑州中心医院转化医学中心
    4. 450007 郑州大学附属郑州中心医院肿瘤内科
  • 收稿日期:2017-09-27 出版日期:2018-06-25
  • 通信作者: 李学民, 王晓飞
  • 基金资助:
    2014年度河南省医学科技攻关计划(No.201403269); 2015年度河南省高等学校重点科研项目(No.15A320025)

Influence of drug transporters polymorphisms on severe adverse reaction caused by irinotecan in colorectal cancer patients

Chao Ma1, Yan Jin2, Xibin Duan1, Wei Cao3, Guochen Xing4, Shanyong Yi4, Xuemin Li1,(), Xiaofei Wang3,()   

  1. 1. Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
    2. Department of Breast and Thyroid Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
    3. Translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
    4. Department of Oncology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
  • Received:2017-09-27 Published:2018-06-25
  • Corresponding author: Xuemin Li, Xiaofei Wang
  • About author:
    Corresponding author: Li Xuemin, Email:
    Wang Xiaofei, Email:
引用本文:

马超, 金焰, 段希斌, 曹巍, 邢国臣, 易善永, 李学民, 王晓飞. 药物转运体基因多态性对伊立替康治疗结直肠癌患者所致严重不良反应的影响[J]. 中华结直肠疾病电子杂志, 2018, 07(03): 257-261.

Chao Ma, Yan Jin, Xibin Duan, Wei Cao, Guochen Xing, Shanyong Yi, Xuemin Li, Xiaofei Wang. Influence of drug transporters polymorphisms on severe adverse reaction caused by irinotecan in colorectal cancer patients[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2018, 07(03): 257-261.

目的

本研究旨在探讨药物转运体(ABCB1-3435C>T和ABCC2-24C>T)基因多态性与伊立替康治疗结直肠癌患者严重不良反应(主要指3~4级迟发型腹泻和中性粒细胞减少)的关系。

方法

选取郑州市中心医院结直肠癌患者91例,采集外周静脉血,通过PCR-直接测序法对ABCB1-3435C>T和ABCC2-24C>T多态性进行基因分型,记录化疗中出现的不良反应,比较不同基因型患者使用伊立替康后严重化疗毒性的发生情况。

结果

在结直肠癌患者中,ABCC2-24C>T基因多态性对伊立替康所致严重的迟发性腹泻有影响(χ2=5.067,P=0.024),对中性粒细胞减少无影响(χ2=3.107,P=0.078),而ABCB1-3435C>T基因多态性对伊立替康所致严重的迟发性腹泻和中性粒细胞减少均无影响(分别χ2=0.237,χ2=2.139,P均>0.05)。

结论

ABCC2-24C>T基因多态性可增加结直肠癌患者伊立替康所致严重不良反应的风险,使用伊立替康前,进行ABCC2-24C>T检测,可以减少伊立替康毒副作用。

Objective

To investigate the influence of drug transporters (ABCB1-3435C>T and ABCC2-24C>T) polymorphisms on severe adverse reaction (mainly refers to grade 3~4 delayed diarrhea and neutropenia) caused by irinotecan in colorectal cancer patients.

Methods

A total of 91 colorectal cancer patients from Zhengzhou Central Hospital Affiliated to Zhengzhou University were enrolled in this study. Peripheral venous blood were collected. The genetic polymorphisms of ABCB1-3435C>T and ABCC2-24C>T were analyzed by PCR-Sanger sequence. The adverse reaction during chemotherapy were observed and recorded. The differences of the incidence of grade 3~4 adverse reaction were compared in patients with different genotypes.

Results

There is effect of ABCC2-24C>T polymorphisms on severe delayed diarrhea (χ2=5.067, P=0.024) but not neutropenia (χ2=3.107, P=0.078) in colorectal cancer patients. However, ABCB1-3435C>T polymorphisms don′t affect the severe adverse reaction caused by irinotecan (χ2=0.237, χ2=2.139, all P>0.05).

Conclusion

ABCC2-24C>T but not ABCB1-3435C>T mutation is related to severe toxicity caused by irinotecan in colorectal cancer patients. It can reduce severe adverse reaction that detecting ABCC2-24C>T mutation before using irinotecan.

表1 受试者ABCB1-3435C>T和ABCC2 -24C>T基因型及等位基因分布频率
表2 ABCB1-3435C>T和ABCC2 -24C>T基因多态性与伊立替康所致严重不良反应的关系
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