Rho GTPases: RAC1 polymorphisms affected platinum-based chemotherapy toxicity in lung cancer patients.
OBJECTIVE
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.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Ting
T
Zou
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
Jiye
J
Yin
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Wei
W
Zheng
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Ling
L
Xiao
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Liming
L
Tan
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
Juan
J
Chen
The Affiliated Cancer Hospital of XiangYa School of Medicine, Central South University, Changsha, 410014, People's Republic of China.
Ying
Y
Wang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Xiangping
X
Li
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Chenyue
C
Qian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Jiajia
J
Cui
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
Wei
W
Zhang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
Honghao
H
Zhou
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. liuzhaoqian63@126.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China. liuzhaoqian63@126.com.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China. liuzhaoqian63@126.com.
Zhaoqian
Z
Liu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
D006360:Heat-Shock Proteins; D017671:Platinum Compounds; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein
Genetic polymorphism; Lung cancer; Platinum-based chemotherapy; RAC1; Toxicity