title: Functional PstI/RsaI polymorphism in CYP2E1 is associated with the development, progression and poor outcome of gastric cancer.
abstract: BACKGROUND
  Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development and progression of cancers. It has demonstrated that CYP2E1 polymorphisms alter the transcriptional activity of the gene. However, studies on the association between CYP2E1 polymorphisms (PstI/RsaI or DraI) and gastric cancer have reported conflicting results. Thus, the aim of the present study was to investigate whether CYP2E1 polymorphisms is associated with the development and progression of gastric cancer and its prognosis in Chinese patients.
  
  
  METHODS
  A case-control study was conducted in which CYP2E1 PstI/RsaI and DraI polymorphisms were analyzed in 510 Chinese patients with gastric cancer and 510 age- and sex- matched healthy controls by PCR-RFLP. Odds ratios were estimated by multivariate logistic regression, and the lifetime was calculated by Kaplan-Meier survival curves. In addition, a meta-analysis was also conducted to verify the findings.
  
  
  RESULTS
  For CYP2E1 PstI/RsaI polymorphism, C2C2 homozygotes (OR = 2.15; CI: 1.18-3.94) and C2 carriers (OR = 1.48; CI: 1.13-1.96) were associated with an increased risk of gastric cancer when compared with C1C1 homozygotes. Both C1C2 and C2C2 genotypes were associated with advanced stage, but not the grade of gastric cancer. Moreover, C2C2 genotype was identified as an independent marker of poor overall survival for gastric cancer. However, there was not any significant association between CYP2E1 DraI polymorphism and the risk of gastric cancer. In the meta-analysis, pooled data from 13 studies confirmed that the CYP2E1 PstI/RsaI polymorphism was associated with a significantly increased risk of gastric cancer.
  
  
  CONCLUSIONS
  CYP2E1 PstI/RsaI polymorphism is associated with increased risk of development, progression and poor prognosis of gastric cancer in Chinese patients. Pooled data from 13 studies, mainly in Asian countries, are in agreement with our findings.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Feng
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Pan
authors.forename: Junbo
authors.initials: J
authors.lastname: Yu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012044:Regression Analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D019392:Cytochrome P-450 CYP2E1; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases