title: Effect of hENT1 polymorphism G-706C on clinical outcomes of gemcitabine-containing chemotherapy for Chinese non-small-cell lung cancer patients.
abstract: OBJECTIVE
  To identify the single-nucleotide polymorphism (SNP) of hENT1 G-706C that is associated with response to gemcitabine-containing chemotherapy, and to determine the prognosis in patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with stage III (A+B) or IV NSCLC were recruited for this study (n=225). Each subject received gemcitabine-containing chemotherapy. The association between human equilibrative nucleoside transporter 1 (hENT1) polymorphism G-706C (rs61758845) and therapeutic effect was evaluated. The SNP hENT1 G-706C was genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays.
  
  
  RESULTS
  The polymorphic genotype and the allele frequency of hENT1 G-706C was significantly different between chemotherapy responders and non-responders; to be specific, the response rate of patients carrying an hENT1-706 GG allele was higher than that of patients with a GC or CC genotype. Logistic regression analysis showed that having the GC or CC genotypes was associated with a higher risk of being a non-responder compared with having the GG genotype (OR=2.34, 95% CI: 1.14-4.80; P=0.02). The overall survival in patients with the GG genotype was significantly longer than in those with GC or CC genotype (19.0 versus 15.1 months, P<0.001). The hazard ratio for the (GC+CC) genotype was 1.89 (95% CI: 1.23-2.90) compared with GG carriers (P=0.004).
  
  
  CONCLUSIONS
  The hENT1 genetic polymorphism of hENT1 G-706C was associated with response to the gemcitabine-containing chemotherapy and prognosis of NSCLC. Moreover, assaying this SNP in blood cells may represent a valuable biomarker for individualized treatment for NSCLC patients.
authors.affiliation: Department of Oncology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province 222002, China. Electronic address: wufenglei9@gmail.com.
authors.forename: Fenglei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an Jiangsu 223300, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province 222002, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province 210008, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Tongpeng
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Oncology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province 222002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oncology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province 222002, China. Electronic address: zhengyitong77@126.com.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Chemotherapy response; Non-small-cell lung cancer; Polymorphism; hENT1