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

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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.

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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).

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

    Ting Zou, Jiye Yin, Wei Zheng, Ling Xiao, Liming Tan, Juan Chen, Xiangping Li, Chenyue Qian, Jiajia Cui, Wei Zhang, Honghao Zhou & Zhaoqian Liu

  2. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People’s Republic of China

    Ting Zou, Jiye Yin, Wei Zheng, Ling Xiao, Liming Tan, Juan Chen, Xiangping Li, Chenyue Qian, Jiajia Cui, Wei Zhang, Honghao Zhou & Zhaoqian Liu

  3. Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People’s Republic of China

    Jiye Yin, Juan Chen, Wei Zhang, Honghao Zhou & Zhaoqian Liu

  4. The Affiliated Cancer Hospital of XiangYa School of Medicine, Central South University, Changsha, 410014, People’s Republic of China

    Ying Wang

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  1. Ting Zou
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Correspondence to Zhaoqian Liu.

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Zou, T., Yin, J., Zheng, W. et al. Rho GTPases: RAC1 polymorphisms affected platinum-based chemotherapy toxicity in lung cancer patients. Cancer Chemother Pharmacol 78, 249–258 (2016). https://doi.org/10.1007/s00280-016-3072-0

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