Risk Factors

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.

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 premaligant 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 = 3.1 (95% confidence interval, 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).

Prevention of gastric cancer via eradication of H. pylori infection is being actively considered in several countries.[9-13] Many questions remain unanswered concerning the natural history of H. pylori infection; the mechanism of transmission and the rates of reinfection or recrudescence for different populations are unknown.[14,15] Since about half of the world population is infected, antibacterial treatment seems impractical. Vaccination against H. pylori is very effective in experimental animals, but thus far such efficacy has not been studied in humans. Prevention randomized trials are also under way and might soon indicate whether curing H. pylori infection reduces cancer rates or stops the progression of precancerous lesions.

References

1. Stomach. In: World Cancer Research Fund., American Institute for Cancer Research.: Food, Nutrition and the Prevention of Cancer: A Global Perspective. Washington, DC: The Institute, 1997, pp 148-175. 
   
   
2. Buiatti E, Palli D, Decarli A, et al.: A case-control study of gastric cancer and diet in Italy: II. Association with nutrients. Int J Cancer 45 (5): 896-901, 1990.  [PUBMED Abstract]
   
   
3. Blot WJ, Li JY, Taylor PR, et al.: Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 85 (18): 1483-92, 1993.  [PUBMED Abstract]
   
   
4. Plummer M, Vivas J, Lopez G, et al.: Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. J Natl Cancer Inst 99 (2): 137-46, 2007.  [PUBMED Abstract]
   
   
5. Taylor PR: Prevention of gastric cancer: a miss. J Natl Cancer Inst 99 (2): 101-3, 2007.  [PUBMED Abstract]
   
   
6. Malila N, Taylor PR, Virtanen MJ, et al.: Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland). Cancer Causes Control 13 (7): 617-23, 2002.  [PUBMED Abstract]
   
   
7. Correa P, Fontham ET, Bravo JC, et al.: Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst 92 (23): 1881-8, 2000.  [PUBMED Abstract]
   
   
8. Wong BC, Lam SK, Wong WM, et al.: Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 291 (2): 187-94, 2004.  [PUBMED Abstract]
   
   
9. Nomura A, Stemmermann GN, Chyou PH, et al.: Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325 (16): 1132-6, 1991.  [PUBMED Abstract]
   
   
10. Parsonnet J, Friedman GD, Vandersteen DP, et al.: Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325 (16): 1127-31, 1991.  [PUBMED Abstract]
    
    
11. Forman D, Newell DG, Fullerton F, et al.: Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ 302 (6788): 1302-5, 1991.  [PUBMED Abstract]
    
    
12. Parsonnet J, Harris RA, Hack HM, et al.: Modelling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials. Lancet 348 (9021): 150-4, 1996.  [PUBMED Abstract]
    
    
13. Miehlke S, Kirsch C, Dragosics B, et al.: Helicobacter pylori and gastric cancer:current status of the Austrain Czech German gastric cancer prevention trial (PRISMA Study). World J Gastroenterol 7 (2): 243-7, 2001.  [PUBMED Abstract]
    
    
14. Cheung TK, Xia HH, Wong BC: Helicobacter pylori eradication for gastric cancer prevention. J Gastroenterol 42 (Suppl 17): 10-5, 2007.  [PUBMED Abstract]
    
    
15. de Vries AC, Haringsma J, Kuipers EJ: The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection. Helicobacter 12 (1): 1-15, 2007.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >