Abstract
Manganese superoxide dismutase is the primary antioxidant enzyme in the mitochondria and is involved in carcinogenesis. To investigate the association between MnSOD Val(16)Ala polymorphism and risk of advanced gastric lesions, and its effects on chemoprevention, a population-based study was conducted in Linqu, a high-risk area of gastric cancer in China. Genotypes were determined by PCR-RFLP analysis in 3,355 subjects with the baseline histopathologic diagnosis in 1994, and 2,758 of these subjects received subsequent three interventions including vitamin supplementation for 7.3 years. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression model. We found an increased risk of dysplasia in subjects with the Val/Ala+Ala/Ala genotype (OR, 1.31; 95% CI, 1.02-1.68) compared with the Val/Val genotype. Stratified analysis indicated that a significantly elevated risk of intestinal metaplasia (OR, 3.40; 95% CI, 2.64-4.38) or dysplasia (OR, 4.01; 95% CI, 2.79-5.74) was found in subjects carrying the Val/Ala+Ala/Ala genotype and Helicobacter pylori infection, and an interaction between this genotype and a high serum H. pylori IgG titer (>2.94) on the risk of dysplasia was observed (P(interaction) = 0.01). Furthermore, an elevated chance for regression of gastric lesions was observed in subjects with the Val/Ala+Ala/Ala genotype and high IgG titer in an intervention trial with vitamin supplementation (OR, 2.45; 95% CI, 1.37-4.38). These findings suggest that Val(16)Ala polymorphism may play an important role in development of advanced gastric lesions and modify the effect of vitamin supplementation on the evolution of gastric lesions. Val(16)Ala polymorphism is related to gastric cancer development.
Highlights
Oxidative stress caused by the generation of reactive oxygen species (ROS) is involved in carcinogenesis [1]
We further evaluated the possible interaction between Val16Ala polymorphism and H. pylori density, which was indicated by levels of serum H. pylori IgG titer in current study, and found a significantly increased risk of advanced gastric lesions in subjects with the combined Val/Ala+Ala/Ala genotype and high serum H. pylori IgG titer (>2.94)
Our results suggest that Val16Ala polymorphism may play an important role in the development of advanced gastric lesions and may modify the effect of vitamin supplementation on the evolution of gastric lesions
Summary
Oxidative stress caused by the generation of reactive oxygen species (ROS) is involved in carcinogenesis [1]. This stressful condition may appear due to antioxidant depletion, exposure to toxic agents, or pathologic pro-. A previous study showed that the Ala form of MnSOD allows more efficient MnSOD transport into the mitochondria matrix and generates more active MnSOD compared with the Val form [6]. Val16Ala polymorphism www.aacrjournals.org had an impact on the effect of antioxidant supplementation. To investigate the association between MnSOD Val16Ala polymorphism and risk of advanced gastric lesions, and its effects on chemoprevention, a population-based study was conducted in Linqu, a high-risk area of gastric cancer in China
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