Gastric cancer: Prevention - Health Professional Information [NCI PDQ]

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about gastric cancer prevention. This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board.

Information about the following is included in this summary:

• Gastric cancer incidence and mortality statistics and information about gastric cancer risk factors.
• Interventions for gastric cancer prevention.

This summary is intended as a resource to inform clinicians and other health professionals about the currently available information on gastric cancer prevention. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in reporting the evidence of benefit and potential harms associated with specific interventions. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version, which is written in less technical language.

Note: Separate PDQ summaries on Stomach (Gastric) Cancer Screening, Gastric Cancer Treatment, and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Dietary Factors

Based on fair evidence, excessive salt intake and deficient dietary consumption of fresh fruits and vegetables are associated with an increased risk of gastric cancer. Dietary intake of vitamin C contained in vegetables, fruits, and other foods of plant origin is associated with a reduced risk of gastric cancer. Diets high in whole-grain cereals, carotenoids, allium compounds, and green tea are also associated with a reduced risk of this cancer. However, it is uncertain if changing one's diet to include more vegetables, fruits, and whole grains would reduce the risk of gastric cancer.

Description of the Evidence

• STUDY DESIGN: Evidence obtained from cohort or case-control studies.
• INTERNAL VALIDITY: Good.
• CONSISTENCY: Small number of studies.
• MAGNITUDE OF EFFECTS ON HEALTH OUTCOMES: Small, difficult to determine.
• EXTERNAL VALIDITY: Fair (populations vary greatly in their underlying nutritional status).

Helicobacter Pylori Infection

Based on solid evidence, Helicobacter pylori infection is associated with an increased risk of gastric cancer, however, the evidence is inadequate to determine if treatment with antibiotics reduces the risk of developing gastric cancer.

Description of the Evidence

• STUDY DESIGN: Evidence obtained from cohort or case-control studies.
• INTERNAL VALIDITY: Good.
• CONSISTENCY: Good, multiple studies.
• MAGNITUDE OF EFFECTS ON HEALTH OUTCOMES: Increased risk, moderate magnitude.
• EXTERNAL VALIDITY: Good.

Chemoprevention

The evidence is inadequate to determine if dietary or antibiotic interventions will reduce the risk of developing gastric cancer. A chemoprevention trial in China reported a statistically significant reduction of gastric cancer mortality after supplementation with beta carotene, vitamin E, and selenium.

Description of the Evidence

• STUDY DESIGN: Evidence obtained from randomized controlled trials.
• INTERNAL VALIDITY: Fair.
• CONSISTENCY: Poor.
• MAGNITUDE OF EFFECTS ON HEALTH OUTCOMES: Cannot determine.
• EXTERNAL VALIDITY: Fair.

Incidence and Mortality

The age-adjusted incidence rate in the United States for the years 2000 to 2003 was 8.1 per 100,000. Incidence among men is twice as high as among women.[1] Mortality rates for gastric cancer have been declining worldwide in recent decades, most prominently in the United States.[2,3] Mortality rates for white males in the United States were approximately 40 per 100,000 in 1930, compared with 5.8 per 100,000 for the years 1997 to 2001. The death rate from gastric cancer for black males was 2.3-fold higher than for whites for the years 1997 to 2001.[4] The annual number of new cases seems to be steady in recent years; in 2008, it is estimated 21,500 Americans will be diagnosed with gastric cancer and 10,880 will die of it.[5] Worldwide, gastric cancer is the fourth most common cancer.[6] Most cancers in the United States are advanced at diagnosis, which is reflected in an overall 5-year survival of 24.3% from 1996 to 2002.[1] Carcinomas localized to the mucosa or submucosa (“early” cancers) have a much better prognosis: the 5-year survival rate is more than 95% in Japan and more than 65% in the United States. In high-risk populations, secondary prevention measures linked to screening programs have been instituted.[7] In Japan, endoscopic resection techniques have been refined and may be responsible for drastic reductions in mortality rates in the presence of steady incidence rates. This hypothesis, however, has not been tested in clinical trials. (Refer to the PDQ summary on Stomach (Gastric) Cancer Screening for more information.)

Pathogenesis

Our understanding of the pathogenesis of gastric cancer has advanced in recent years. A prolonged precancerous process has been identified in which the gastric mucosa is slowly transformed from normal to chronic gastritis, to multifocal atrophy, to intestinal metaplasia of various degrees, to dysplasia, and finally to invasive carcinoma.[8] The process is apparently driven by forces acting on the gastric epithelium for many years, such as excessive dietary salt and most prominently, infection with Helicobacter pylori.

References:

1. Ries LAG, Harkins D, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2003. Bethesda, Md: National Cancer Institute, 2006. Also available online. Last accessed December 4, 2007.
2. Qiu D, Tanaka S: International comparisons of cumulative risk of stomach cancer, from Cancer Incidence in Five Continents Vol. VIII. Jpn J Clin Oncol 36 (2): 123-4, 2006.
3. Stomach. In: Ries LA, Kosary CL, Hankey BF, et al., eds.: SEER Cancer Statistics Review 1973-1995. Bethesda, Md: National Cancer Institute, 1998, Section 13.
4. American Cancer Society.: Cancer Facts and Figures 2005. Atlanta, Ga: American Cancer Society, 2005. Also available online. Last accessed April 30, 2008.
5. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed February 21, 2008.
6. Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2 (9): 533-43, 2001.
7. Tan YK, Fielding JW: Early diagnosis of early gastric cancer. Eur J Gastroenterol Hepatol 18 (8): 821-9, 2006.
8. Correa P: Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 52 (24): 6735-40, 1992.

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.[9,10,11,12,13] 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.
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.
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.
5. Taylor PR: Prevention of gastric cancer: a miss. J Natl Cancer Inst 99 (2): 101-3, 2007.
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.
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.
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.
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.
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.
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.
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.
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.
14. Cheung TK, Xia HH, Wong BC: Helicobacter pylori eradication for gastric cancer prevention. J Gastroenterol 42 (Suppl 17): 10-5, 2007.
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.

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SIGNIFICANCE

Updated incidence and mortality estimates for 2008 (cited American Cancer Society as reference 5).

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Date Last Modified: 2008-03-13