What are the risk factors for gastric cancer and how can they be mitigated?

Risk Factors for Gastric Cancer and Mitigation Strategies

Helicobacter pylori infection is the most consistent and important risk factor for gastric cancer, and its eradication is the most promising strategy to reduce gastric cancer incidence. 1

Primary Risk Factors

Infectious Factors

• H. pylori infection:
  • Present in 71-95% of all gastric cancers 1
  • Causes chronic gastritis, which progresses to atrophy, intestinal metaplasia, and eventually cancer 1
  • Corpus-dominant H. pylori gastritis carries substantially increased risk 1

Genetic and Family Factors

• Family history:
  • First-degree relatives of gastric cancer patients have 2-3 times increased risk 1
  • Risk increases 10-fold with multiple affected first-degree relatives 1
• Hereditary syndromes:
  • CDH-1 gene mutation (hereditary diffuse gastric cancer) carries 40-70% lifetime risk for men and 60-80% for women 1
  • Represents less than 1% of gastric cancers 1

Preneoplastic Conditions

• Atrophic gastritis 1
• Intestinal metaplasia (IM) - considered irreversible 1
• Severe pan-gastritis or corpus-predominant gastritis 1

Environmental and Lifestyle Factors

• Diet:
  • High salt intake 1
  • Preserved foods 1
  • Low consumption of fresh fruits and vegetables 1, 2
  • Processed meats and red meat 2
  • High dietary fat 2
• Smoking 1
• Heavy alcohol consumption (particularly for non-cardia gastric cancers) 1, 2
• Occupational exposure:
  • Dust, coal, quartz, cement, and quarry work 1
• Long-term acid suppression:
  • Chronic gastric acid inhibition for more than 1 year 1
  • Proton pump inhibitors may increase risk through hypochlorhydria 3

Mitigation Strategies

H. pylori Eradication

• Early eradication is most effective before development of preneoplastic conditions 1
• Target populations for screening and eradication:
  • First-degree relatives of gastric cancer patients 1
  • Patients with previous gastric neoplasia 1
  • Patients with atrophic gastritis or intestinal metaplasia 1
  • Individuals from high-risk regions (first-generation immigrants) 1
  • Non-white racial and ethnic groups in the US 1

Dietary Modifications

• Increase consumption of:
  • Fresh fruits and vegetables (at least five servings per day) 1, 2
  • Foods rich in antioxidants (vitamin C, vitamin E, carotene) 1
  • Whole grains and nuts 2
• Reduce consumption of:
  • Salt and salty foods 1, 2
  • Processed meats 2
  • Red meat 2
  • High-fat foods 2

Lifestyle Changes

• Smoking cessation 1
• Moderate alcohol consumption 1, 2
• Regular physical activity to maintain healthy weight 4

Surveillance for High-Risk Individuals

• Endoscopic screening for early detection 1
• Risk stratification based on:
  • Severity and distribution of preneoplastic lesions 1
  • Family history 1
  • Ethnic background 1
• OLGA/OLGIM staging systems to assess gastritis progression and cancer risk 1

Implementation of Prevention Strategies

Primary Prevention Algorithm

1. Identify high-risk individuals:

   • First-degree relatives of gastric cancer patients
   • Individuals from high-incidence regions
   • Those with preneoplastic conditions
   • Individuals with strong environmental risk factors

2. Test for H. pylori using validated serological tests or other appropriate methods 1

3. Eradicate H. pylori if positive, using antibiotic combinations based on local resistance patterns 1

4. Recommend dietary and lifestyle modifications:

   • Increase fruits, vegetables, whole grains
   • Decrease salt, processed foods, red meat
   • Quit smoking
   • Limit alcohol consumption

Secondary Prevention Algorithm

1. Risk stratification based on presence of:

   • Family history
   • Preneoplastic conditions
   • H. pylori status

2. Endoscopic surveillance for those with:

   • Atrophic gastritis
   • Intestinal metaplasia
   • Family history of gastric cancer
   • Previous gastric neoplasia

3. Follow-up intervals based on risk level and findings

Important Caveats

• Intestinal metaplasia is generally considered irreversible, even after H. pylori eradication 1
• Gastric atrophy may be reversible in the corpus but not in the antrum 1
• H. pylori eradication is most effective before development of preneoplastic conditions 1
• Screening strategies should be tailored to population risk and available resources 1
• Antibiotic resistance is a growing concern for H. pylori eradication 1