Evidence of Benefit
Risk Factors
Excessive salt intake has been identified as a possible risk factor for gastric cancer in many correlation studies and many case-control studies.[1,2] The daily intake of sodium chloride, however, has decreased drastically in most western countries and in Japan, in part due to public health campaigns to reduce hypertensive diseases. This may be at least partially responsible for declines in gastric cancer rates. There is a strong association between high salt intake and risk of gastric cancer.
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Epidemiologic evidence suggests that increased intake of fresh fruits and vegetables is associated with decreased gastric cancer rates.[2] This has been borne out by numerous case-control and cohort studies of gastric cancer. Dietary indices of micronutrient intake have been calculated and indicate possible protective effects of beta carotene and vitamin C or foods that contain these compounds. A chemoprevention trial in China reported a statistically significant reduction of gastric cancer mortality rate after supplementation with beta carotene, vitamin E, and selenium.[3] The population studied, however, may have been nutritionally deficient, raising questions of generalizability to other populations such as that of the United States. In addition, the experimental design did not permit assessment of the relative effects of beta carotene, vitamin E, and selenium. In a randomized double-blind chemoprevention trial in Venezuela among a population at increased risk for gastric cancer, a combination of antioxidant vitamins (vitamins C, E, and beta carotene) failed to modify progression or regression of precancerous gastric lesions.[4] Another potential explanation for the lack of benefit of vitamin supplementation in this trial was the high prevalence of advanced premalignant lesions and the rate of Helicobacter pylori infection.[5]
A secondary analysis of the Alpha-Tocopherol Beta Carotene trial conducted among male smokers in Finland evaluated the effect of supplementation on gastric cancer incidence.[6] No protective effects for these supplements against gastric cancer were observed. Six-year follow-up results of a study of 976 Colombian patients have been reported. Patients were randomly assigned to receive eight different treatments that included vitamin supplements and anti-Helicobacter therapy either alone or in combination versus placebo. Among the 79 patients who received anti-Helicobacter therapy, a borderline regression of intestinal metaplasia when compared with a placebo (15% vs. 6%; relative risk [RR] = 3.1; 95% confidence interval [CI], 1.0-9.3) was noted. However, the combinations of antibiotics and vitamins did not confer additional benefits. More importantly, the progression rate of intestinal metaplasia was comparable irrespective of the treatments received. The progression rate was 23% in the placebo group and 17% in antibiotic recipients.[7]
A randomized clinical trial evaluating the effect of eradicating H. pylori infection was conducted in a high-risk area of China.[8] Otherwise healthy carriers of H. pylori were randomly assigned either to a 2-week course of antibiotic therapy with omeprazole, a combination of amoxicillin and clavulanate potassium, and metronidazole (N = 817), or to a placebo (N = 813). After a 7.5-year follow-up, gastric cancer was not reduced in the treatment arm (7 vs. 11 cases; P = .33). In a subgroup analysis among those free of precancerous lesions at study entry, a statistically significant reduction in development of gastric cancer was observed in the treatment arm compared with placebo (0 vs. 6 cases; P = .02).
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