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

被引：14

作者：

Zou, Ting ^{[1
,2
]}

Yin, Jiye ^{[1
,2
,3
]}

Zheng, Wei ^{[1
,2
]}

Xiao, Ling ^{[1
,2
]}

Tan, Liming ^{[1
,2
]}

Chen, Juan ^{[1
,2
,3
]}

Wang, Ying ^{[4
]}

Li, Xiangping ^{[1
,2
]}

Qian, Chenyue ^{[1
,2
]}

Cui, Jiajia ^{[1
,2
]}

Zhang, Wei ^{[1
,2
,3
]}

Zhou, Honghao ^{[1
,2
,3
]}

Liu, Zhaoqian ^{[1
,2
,3
]}

机构：

[1] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Hunan, Peoples R China

[2] Cent South Univ, Inst Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha 410078, Hunan, Peoples R China

[3] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China

[4] Cent South Univ, XiangYa Sch Med, Affiliated Canc Hosp, Changsha 410014, Hunan, Peoples R China

来源：

CANCER CHEMOTHERAPY AND PHARMACOLOGY | 2016年 / 78卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Lung cancer; Platinum-based chemotherapy; Toxicity; Genetic polymorphism; RAC1; HEAT-SHOCK PROTEINS; P21-ACTIVATED KINASES; BREAST-CANCER; DNA-DAMAGE; CELL; ASSOCIATION; INHIBITION; EXPRESSION; MUTATIONS; INVASION;

D O I：

10.1007/s00280-016-3072-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. 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. 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). 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.

引用

页码：249 / 258

页数：10

共 40 条

[1] Alan Jamie K, 2013, Small GTPases, V4, P159, DOI 10.4161/sgtp.26530
[2] Alvarez Diego E, 2015, Small GTPases, V6, P119, DOI 10.1080/21541248.2015.1055182
[3] [Anonymous], AFRICAN J TRADITIONA
[4] [Anonymous], TUMOR BIOL
[5] Rho GTPases in platelet function
Aslan, J. E.
Mccarty, O. J. T.
[J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2013, 11 (01) : 35 - 46
[6] Rho signals to cell growth and apoptosis
Aznar, S
Lacal, JC
[J]. CANCER LETTERS, 2001, 165 (01) : 1 - 10
[7] p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase
Barrows, Douglas
Schoenfeld, Sarah M.
Hodakoski, Cindy
Silkov, Antonina
Honig, Barry
Couvillon, Anthony
Shymanets, Aliaksei
Nuernberg, Bernd
Asara, John M.
Parsons, Ramon
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (48) : 28915 - 28931
[8] RAC1: An Emerging Therapeutic Option for Targeting Cancer Angiogenesis and Metastasis
Bid, Hemant K.
Roberts, Ryan D.
Manchanda, Parmeet K.
Houghton, Peter J.
[J]. MOLECULAR CANCER THERAPEUTICS, 2013, 12 (10) : 1925 - 1934
[9] The Evolution of Therapies in Non-Small Cell Lung Cancer
Boolell, Vishal
Alamgeer, Muhammad
Watkins, David N.
Ganju, Vinod
[J]. CANCERS, 2015, 7 (03) : 1815 - 1846
[10] Evidence for a functional genetic polymorphism of the Rho-GTPase Rac1. Implication in azathioprine response?
Bourgine, Joanna
Garat, Anne
Allorge, Delphine
Crunelle-Thibaut, Aurelie
Lo-Guidice, Jean-Marc
Colombel, Jean-Frederic
Broly, Franck
Billaut-Laden, Ingrid
[J]. PHARMACOGENETICS AND GENOMICS, 2011, 21 (06) : 313 - 324

← 1 2 3 4 →