The association of transporter genes polymorphisms and lung cancer chemotherapy response

Ying Wang; Ji-Ye Yin; Xiang-Ping Li; Juan Chen; Chen-Yue Qian; Yi Zheng; Yi-Lan Fu; Zi-Yu Chen; Hong-Hao Zhou; Zhao-Qian Liu

doi:10.1371/journal.pone.0091967

The association of transporter genes polymorphisms and lung cancer chemotherapy response

PLoS One. 2014 Mar 18;9(3):e91967. doi: 10.1371/journal.pone.0091967. eCollection 2014.

Authors

Affiliations

¹ Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, P. R. China.
² The Affiliated Cancer Hospital of XiangYa School of Medicine, Central South University, Changsha, Hunan, P. R. China.

Abstract

Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transporters OCT2, LRP, AQP2, AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients. The rs195854 in genotypic model, rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response. In stratification analysis, TMEM205 rs896412, OCT2 rs1869641 and rs195854, AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response. In conclusion, the genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Agents / therapeutic use*
Aquaporin 2 / genetics
Aquaporins / genetics
Carboplatin / therapeutic use
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Cisplatin / therapeutic use
Drug Resistance, Neoplasm / genetics
Female
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Male
Membrane Proteins / genetics
Middle Aged
Models, Genetic
Organic Cation Transport Proteins / genetics
Organic Cation Transporter 2
Polymorphism, Single Nucleotide*
Response Evaluation Criteria in Solid Tumors
Small Cell Lung Carcinoma / drug therapy
Small Cell Lung Carcinoma / genetics*
Small Cell Lung Carcinoma / pathology
Treatment Outcome

Substances

AQP2 protein, human
AQP9 protein, human
Antineoplastic Agents
Aquaporin 2
Aquaporins
Membrane Proteins
Organic Cation Transport Proteins
Organic Cation Transporter 2
SLC22A2 protein, human
TMEM205 protein, human
Carboplatin
Cisplatin

Grants and funding

This work was supported in part by National High-tech R&D Program of China 863 Program Grant 2012AA02A517 (ZYC)(http://www.863.gov.cn/), National Natural Science Foundation of China Grants 81173129 and 81373490 (ZYC), and 81202595 (JY)(http://scholarmate.nsfc.gov.cn/scm/), Program for the Special Scientific Research Foundation of Doctor Disciplines in University of Ministry of Education of China Grant 20110162110034 (ZYC), Hunan Provincial Natural Science Foundation of China Grant 12JJ7006 (ZYC)(http://www.hnst.gov.cn/zxgz/zkjj/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.