Document Detail

Functional alterations in the glutathione S-transferase family associated with enhanced occurrence of esophageal carcinoma in China.
MedLine Citation:
PMID:  20391126     Owner:  NLM     Status:  MEDLINE    
Glutathione S-transferases (GST) belong to a superfamily of phase II enzymes believed to be associated with enhanced frequency of esophageal carcinoma. This study was performed to evaluate whether the GST family was associated with susceptibility to esophageal carcinoma in China. Ninety-seven patients with newly diagnosed, untreated esophageal squamous-cell carcinoma (ESCC) and 97 healthy controls matched in age, gender, and residence were recruited in this community-based case-control study. Null genotypes of GSTM1 and GSTT1 were determined by multiplex polymerase chain reaction (PCR) technique. Ile105Val polymorphism in the fifth exon, mRNA level, CpG island hypermethylation of promoter, and protein levels of GSTP1 gene were measured with peripheral blood mononuclear cell (PBMC) by PCR-restriction fragment length polymorphism (PCR-RFLP) techniques, quantitative real-time reverse transcription PCR, methylation-specific PCR (MSP), and Western blotting, respectively. The results showed that GSTM1 null genotype and GSTT1 null genotype were significantly associated with increased risk for esophageal cancer in Chinese population. Compared with the control, the relative expression levels of mRNA were significantly reduced in ESCC patients. The conditional logistic regression analysis demonstrated that increased risk for esophageal cancer was associated with CpG island hypermethylation of promoter of GSTP1 gene. GSTP1 protein levels also showed significant decrease in ESCC when adjusted for age, gender, smoking status, and alcohol use. An individual with GSTM1 or GSTT1 null genotype may thus be more susceptible to esophageal cancer development. Reduced expression in mRNA and protein levels were the main manifestations noted in aberrant function of GSTP1 gene. Data thus suggest that the CpG island hypermethylation of promoter gene may serve as a useful biomarker for early diagnosis of esophageal carcinoma development.
Ran Liu; Lihong Yin; Yuepu Pu; Yunhui Li; Geyu Liang; Juan Zhang; Xiaobo Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of toxicology and environmental health. Part A     Volume:  73     ISSN:  1528-7394     ISO Abbreviation:  J. Toxicol. Environ. Health Part A     Publication Date:  2010  
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-06-17     Revised Date:  2011-02-02    
Medline Journal Info:
Nlm Unique ID:  100960995     Medline TA:  J Toxicol Environ Health A     Country:  England    
Other Details:
Languages:  eng     Pagination:  471-82     Citation Subset:  IM    
Department of Occupational and Environmental Health, School of Public Health, Southeast University, Nanjing, People's Republic of China.
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MeSH Terms
Carcinoma, Squamous Cell / enzymology,  epidemiology,  genetics*
Case-Control Studies
China / epidemiology
CpG Islands
DNA Methylation
Esophageal Neoplasms / enzymology,  epidemiology,  genetics*
Gene Frequency
Genetic Predisposition to Disease / epidemiology
Glutathione S-Transferase pi / genetics,  metabolism
Glutathione Transferase / genetics*,  metabolism
Middle Aged
Polymorphism, Single Nucleotide
Reg. No./Substance:
EC 2.5.1.-/glutathione S-transferase T1; EC protein, human; EC S-Transferase pi; EC Transferase; EC S-transferase M1

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