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Cancer Chemotherapy and Pharmacology

, Volume 78, Issue 2, pp 249–258 | Cite as

Rho GTPases: RAC1 polymorphisms affected platinum-based chemotherapy toxicity in lung cancer patients

  • Ting Zou
  • Jiye Yin
  • Wei Zheng
  • Ling Xiao
  • Liming Tan
  • Juan Chen
  • Ying Wang
  • Xiangping Li
  • Chenyue Qian
  • Jiajia Cui
  • Wei Zhang
  • Honghao Zhou
  • Zhaoqian LiuEmail author
Original Article

Abstract

Purpose

Lung cancer is the leading cause of cancer deaths in the world. The toxicity of platinum-based chemotherapy is a main reason limiting its clinical effects. RAC1, as a member of the Rho family of small guanosine triphosphatases (GTPases), was reported to be related to most cancers, such as breast cancer, gastric cancer, testicular germ cell cancer, and lung cancer. Its potential of becoming a drug target in cancer treatment has been investigated in recent years. The aim of this study was to investigate the association between genetic polymorphisms and platinum-based chemotherapy toxicity.

Methods

We enrolled 317 lung cancer patients randomly. Nineteen polymorphisms of HSP genes and Rho family genes were genotyped by Sequenom MassARRAY. The logistic regression was performed by PLINK to compare the relevance of polymorphisms and toxicity outcome.

Results

We found that the polymorphisms of RAC1 rs836554, rs4720672, and rs12536544 were significantly associated with platinum-based chemotherapy toxicity (p = 0.018, p = 0.044, and p = 0.021, respectively).

Conclusions

RAC1 rs836554, rs4720672, and rs12536544 polymorphisms may be novel and useful genetic markers to predict the toxicity induced by platinum-based chemotherapy in lung cancer patients.

Keywords

Lung cancer Platinum-based chemotherapy Toxicity Genetic polymorphism RAC1 

Notes

Acknowledgments

This work was supported by the National High-tech R&D Program of China (863 Program) (2012AA02A517), National Natural Science Foundation of China (81373490, 81573508, 81573463), Hunan Provincial Science and Technology Plan of China (2015TP1043), and Open Foundation of Innovative Platform in University of Hunan Province of China (2015-14).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

280_2016_3072_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ting Zou
    • 1
    • 2
  • Jiye Yin
    • 1
    • 2
    • 3
  • Wei Zheng
    • 1
    • 2
  • Ling Xiao
    • 1
    • 2
  • Liming Tan
    • 1
    • 2
  • Juan Chen
    • 1
    • 2
    • 3
  • Ying Wang
    • 4
  • Xiangping Li
    • 1
    • 2
  • Chenyue Qian
    • 1
    • 2
  • Jiajia Cui
    • 1
    • 2
  • Wei Zhang
    • 1
    • 2
    • 3
  • Honghao Zhou
    • 1
    • 2
    • 3
  • Zhaoqian Liu
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Clinical Pharmacology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Institute of Clinical Pharmacology, Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Hunan Province Cooperation Innovation Center for Molecular Target New Drug StudyHengyangPeople’s Republic of China
  4. 4.The Affiliated Cancer Hospital of XiangYa School of MedicineCentral South UniversityChangshaPeople’s Republic of China

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