title: Prediction of copper transport protein 1 (CTR1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (NSCLC) patients.
abstract: BACKGROUND
  Cisplatin toxicity severely obstacles successful chemotherapy in lung cancer patients. Cisplatin uptake is considered as one of the major factors contributing to the side effects of cisplatin. Genetic variances of core genes also affect cisplatin toxicity. It has been identified that CTR1, copper transporter protein 1, plays an essential role in cisplatin uptake. The purpose of this study is to investigate whether CTR1 polymorphism is associated with platinum toxicity in non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  204 incident NSCLC patients from three different institutions were enrolled and followed up. These patients were histologically confirmed with non-small cell lung cancer. All patients have accepted cisplatin-based chemotherapy for at least two cycles. Twenty SNPs of CTR1 were detected in these patients.
  
  
  RESULTS
  CTR1 rs10981694 A>C polymorphism is associated with cisplatin induced severe toxicity in NSCLC patients. C-carrier subjects presented poorer tolerance to ototoxicity (p<0.05). The survival times of patients with different rs10981694 genetic polymorphism were not significantly different.
  
  
  CONCLUSIONS
  NSCLC patients carrying C allele of CTR1 rs10981694 presented more sensitivity to ototoxicity after cisplatin treatment. CTR1 plays an essential role in cisplatin toxicity and could be considered as a predictor for pretreatment evaluation in lung cancer patients.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan Province, 410078, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.forename: Huayi
authors.initials: H
authors.lastname: Ren
authors.forename: Boting
authors.initials: B
authors.lastname: Zhou
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ruixia
authors.initials: R
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhaoqian
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D027682:Cation Transport Proteins / Q000235:genetics*; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D000079923:Copper Transporter 1; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D002945:Cisplatin