Summary of Evidence

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.

Smoking

Based on solid evidence, smoking is associated with an increased risk of stomach cancer.[1,2,3] Based on the 2004 Surgeon General's report, cigarette smoking is a cause of stomach cancer, with an average relative risk (RR) in former smokers of 1.2 and in current smokers of 1.6.[4] Compared to persistent smokers, the risk of stomach cancer decreases among former smokers with time since cessation. This pattern of observations makes it reasonable to infer that cigarette smoking prevention or cessation would result in a decreased risk of gastric cancer.

• Study Design: Evidence obtained from case-control and cohort studies.
• Internal Validity: Good.
• Consistency: Good.
• Magnitude of Effects on Health Outcomes: A systematic review and meta-analysis showed a 60% increase in gastric cancer in male smokers and a 20% increase in gastric cancer in female smokers compared to nonsmokers.[1]
• External Validity: Good.

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, H. pylori infection is associated with an increased risk of gastric cancer. A meta-analysis of seven studies mostly done in Asia suggests that treatment of H. pylori may reduce gastric cancer risk (from 1.7% to 1.1%), decreasing RR to 0.65 (95% confidence interval, 0.43–0.98).[5] Only two studies assessed gastric cancer incidence, and two different studies were double-blinded. It is unclear how generalizable the results may be to the North American population.

Description of the Evidence

• Study Design: Randomized controlled trials of H. pylori eradication.
• Internal Validity: Good.
• Consistency: Good.
• Magnitude of Effects on Health Outcomes: Risk of cancer may be reduced; effect on cancer mortality is not known.
• 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.

References:

Significance

Incidence and Mortality

The age-adjusted incidence rate in the United States for the years 2004 to 2008 was 7.7 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 4.6 per 100,000 for the years 2003 to 2007. The death rate from gastric cancer for black males was 2.3-fold higher than for whites for the years 2003 to 2007.[4] The annual number of new cases seems to be steady in recent years; in 2011, it is estimated 21,520 Americans will be diagnosed with gastric cancer and 10,340 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 27.1% from 2001 to 2007.[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 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:

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.

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).

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.

A meta-analysis of seven studies mostly done in Asia suggests that treatment of H. pylori may reduce gastric cancer risk (from 1.7% to 1.1%), decreasing RR to 0.65 (95% CI, 0.43–0.98).[16] Only two studies assessed gastric cancer incidence, and only two were double-blinded studies. It is unclear how generalizable the results may be to the North American population. It would be useful to know which subgroups of persons with H. pylori are particularly likely to develop cancer, to decide which subgroups might be appropriate to consider for targeted screening and eradication.

Smoking

A systematic review and meta-analysis showed a 60% increase in gastric cancer in male smokers and a 20% increase in gastric cancer in female smokers compared to nonsmokers.[17] A systematic review of studies addressing the relationship between cigarette smoking and gastric cancer to estimate the magnitude of the association for different levels of exposure to cancer and provides solid evidence to classify smoking as the most important behavioral risk factor for gastric cancer.[17,18,19]

References:

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Changes to This Summary (07 / 15 / 2011)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Significance

Updated statistics with estimated new cases and deaths for 2011 and Surveillance, Epidemiology, and End Results incidence estimates for 2008 (cited Howlader et al. as reference 1 and American Cancer Society as reference 5).

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About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about stomach (gastric) cancer prevention. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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National Cancer Institute: PDQ® Stomach (Gastric) Cancer Prevention. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/prevention/gastric/HealthProfessional. Accessed <MM/DD/YYYY>.

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Last Revised: 2011-07-15