Manganese superoxide dismutase polymorphism and risk of gastric lesions, and its effects on chemoprevention in a Chinese population.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.


CONCLUSIONS
Val(16)Ala polymorphism is related to gastric cancer development.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, PR China.
Hua-kang
HK
Tu
Kai-feng
KF
Pan
Yang
Y
Zhang
Wen-qing
WQ
Li
Lian
L
Zhang
Jun-ling
JL
Ma
Ji-you
JY
Li
Wei-cheng
WC
You
D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use; D044466:Asian People; D019587:Dietary Supplements; D005260:Female; D005737:Garlic; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology / Q000517:prevention & control; D012643:Selenium / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000235:genetics*; D014810:Vitamin E / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*
D014815:Vitamins; D014810:Vitamin E; D013482:Superoxide Dismutase; D012643:Selenium; D001205:Ascorbic Acid