Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non-small cell lung carcinoma patients.
1. Chemotherapeutic resistance to platinum-based anticancer drugs is a major obstacle in the successful treatment of lung cancer. Cellular uptake and platinum accumulation are considered the most important factors contributing to platinum resistance. The copper transporter family is the major plasma membrane transporter for platinum uptake. Copper transporter protein 1 (CTR1) plays an essential role in cisplatin influx and is closely related to platinum resistance by influencing platinum uptake and accumulation. The aim of the present study was to determine whether CTR1 polymorphisms are associated with platinum resistance in non-small cell lung carcinoma (NSCLC) patients. 2. A total of 282 incident Chinese Han NSCLC patients were enrolled in the study and followed up at three different institutions. All patients underwent at least two cycles of platinum-based chemotherapy. Twenty single-nucleotide polymorphisms of CTR1 were detected from genomic DNA samples. 3. Genetic polymorphisms of CTR1 at rs7851395 and rs12686377 were associated with platinum resistance in NSCLC patients. Patients with a GT haplotype presented with increased susceptibility to platinum resistance (P < 0.05), whereas an AG haplotype contributed to longer survival (P < 0.05). 4. In conclusion, a significant relationship was found between rs7851395 and rs12686377 polymorphisms and platinum resistance, as well as clinical outcomes, in Chinese NSCLC patients. Thus, CTR1 plays an essential role in platinum resistance and could be considered a predictive marker for the pretreatment evaluation of NSCLC patients.
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
Xiaojing
X
Xu
Li
L
Duan
Boting
B
Zhou
Rui
R
Ma
Honghao
H
Zhou
Zhaoqian
Z
Liu
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People; D015415:Biomarkers; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002681:China; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D000079923:Copper Transporter 1; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis
D000970:Antineoplastic Agents; D015415:Biomarkers; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D017671:Platinum Compounds; C490079:SLC31A1 protein, human; D016190:Carboplatin; D002945:Cisplatin