title: Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients.
abstract: OBJECTIVE
  To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients.
  
  
  METHODS
  Twelve tagging SNPs in GST genes (including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom MassARRAY iPLEX genotyping method in a cohort of 214 Chinese patients with resected HCC. The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome. Additionally, stratified analysis was performed at each level of the demographic and clinical variables. An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.
  
  
  RESULTS
  Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively). In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis. We further investigated cumulative effects of these two SNPs on overall survival in HCC patients. Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death (P < 0.001). The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis (HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001). Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variant alleles of rs7085725 (HR = 2.07, 95%CI: 1.13-3.76, P = 0.018). The distributions of GSTO2: rs7085725 and GSTP1: rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.
  
  
  CONCLUSIONS
  Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qu
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Su-Shun
authors.initials: SS
authors.lastname: Liu
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zi-Chao
authors.initials: ZC
authors.lastname: Huang
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Si-Nan
authors.initials: SN
authors.lastname: Liu
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Chang
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xin-Sen
authors.initials: XS
authors.lastname: Xu
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Ya-Feng
authors.initials: YF
authors.lastname: Dong
authors.affiliation: Kai Qu, Su-Shun Liu, Zhi-Xin Wang, Zi-Chao Huang, Si-Nan Liu, Hu-Lin Chang, Xin-Sen Xu, Ting Lin, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006498:Hepatectomy / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C492569:GSTO2 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase
keywords: Clinical outcome; Glutathione S-transferase; Hepatocellular carcinoma; Polymorphism; Surgery