학술논문
No apparent association between genetic polymorphisms (−102 C>T) and (−9 T>C) in the human manganese superoxide dismutase gene and gastric cancer1 .
Document Type
Article
Author
Source
Subject
*GENETIC polymorphisms
*REACTIVE oxygen species
*CANCER cells
*AMINO acids
*
*
*
Language
ISSN
0022-4804
Abstract
Background: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk. This one base pair transition (−9 T>C) leads to a Val to Ala amino acid change in the mitochondrial targeting sequence. In addition, the MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (−102 C>T) has been shown to change the binding pattern of AP-2, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the (−9 T>C) and (−102 C>T) polymorphisms with gastric cancer in a population-based case-control study conducted in Warsaw, Poland. Materials and methods: DNA was obtained from a population based case-control study of stomach cancer conducted in Warsaw, Poland, between 1994 and 1996. The MnSOD –9 T>C genotype was determined by PCR-RFLP assay. The MnSOD –102 C>T genotype was determined using a TaqMan allele discrimination assay. Results: The frequency of the −102 C>T polymorphism was 41% (38/91) in gastric cancer cases and 38% (50/130) in the controls (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.6–2.1). The frequency of the −9 T>C polymorphism was 44% (202/464) in cases and 56% (262/464) in controls (OR 1.1; 95% CI 0.9–1.37). The lack of association was observed in both non-smokers (OR 1.5; 95% CI 0.7–2.34) and smokers (OR 1.1; 95% CI 0.7–1.7). Furthermore, the association was not significant when smokers were segregated by extent of smoking history. Conclusion: The association of the manganese superoxide dismutase polymorphisms at −102 C>T and the −9 T>C were not found to be associated with gastric cancer in a Polish case-control study. [Copyright &y& Elsevier]