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Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2015 Apr 14; Vol. 21 (14), pp. 4310-22. - Publication Year :
- 2015
-
Abstract
- Aim: To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients.<br />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.<br />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.<br />Conclusion: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.
- Subjects :
- Adult
Age Factors
Aged
Aged, 80 and over
Asian People genetics
Carcinoma, Hepatocellular diagnosis
Carcinoma, Hepatocellular enzymology
Carcinoma, Hepatocellular mortality
Carcinoma, Hepatocellular surgery
China epidemiology
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Kaplan-Meier Estimate
Liver Neoplasms diagnosis
Liver Neoplasms enzymology
Liver Neoplasms mortality
Liver Neoplasms surgery
Male
Middle Aged
Phenotype
Proportional Hazards Models
Prospective Studies
Risk Factors
Sex Factors
Smoking adverse effects
Smoking mortality
Time Factors
Treatment Outcome
Young Adult
Carcinoma, Hepatocellular genetics
Glutathione S-Transferase pi genetics
Glutathione Transferase genetics
Hepatectomy adverse effects
Hepatectomy mortality
Liver Neoplasms genetics
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 21
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 25892883
- Full Text :
- https://doi.org/10.3748/wjg.v21.i14.4310