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Functional PstI/RsaI polymorphism in CYP2E1 is associated with the development, progression and poor outcome of gastric cancer.

Feng J, Pan X, Yu J, Chen Z, Xu H, El-Rifai W, Zhang G, Xu Z
PLoS One. 2012 7 (9): e44478

PMID: 22957075 · PMCID: PMC3434136 · DOI:10.1371/journal.pone.0044478

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.

CONCLUSION - 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.

MeSH Terms (20)

Aged Case-Control Studies Cytochrome P-450 CYP2E1 Deoxyribonucleases, Type II Site-Specific Disease Progression Female Gene Expression Regulation, Neoplastic Genotype Homozygote Humans Male Middle Aged Models, Genetic Odds Ratio Polymorphism, Genetic Polymorphism, Restriction Fragment Length Prognosis Regression Analysis Stomach Neoplasms Treatment Outcome

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