What are the risk factors for developing gastric cancer?

Risk Factors for Developing Gastric Cancer

The most significant risk factors for gastric cancer include Helicobacter pylori infection, family history of gastric cancer, dietary factors (high salt, processed foods, low fruit/vegetable intake), smoking, and certain genetic syndromes. 1

Infectious Factors

• H. pylori infection is the most well-established risk factor for gastric cancer, increasing risk approximately 2.5-fold (with some studies showing up to 6-fold increased risk) 1, 2
• H. pylori causes persistent active gastritis that may progress to atrophic gastritis, intestinal metaplasia, and eventually gastric cancer 1, 3
• The risk is higher for non-cardia cancers and possibly with specific pathogenic strains of H. pylori 1

Demographic and Genetic Factors

• Male gender is associated with approximately twice the risk compared to females 1
• Age is a significant risk factor, with peak incidence in the seventh decade of life 1
• Family history of gastric cancer in first-degree relatives increases risk 2-3 fold 1
• Specific genetic syndromes significantly increase risk 1:
  • Hereditary diffuse gastric cancer (HDGC) - associated with CDH1/E-cadherin germline variants
  • Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)
  • Lynch syndrome
  • Familial adenomatous polyposis (FAP)
  • Li-Fraumeni syndrome
  • Peutz-Jeghers syndrome 4

Dietary and Lifestyle Factors

• Diets low in fresh fruits and vegetables increase risk of gastric cancer 1, 5
• High salt consumption is strongly associated with increased risk 1, 5
• Diets high in processed foods, processed meats, and red meat increase risk 1, 5
• Preserved foods with potential carcinogens are risk factors 1, 3
• Smoking increases gastric cancer risk, though the magnitude is less than for lung cancer 1
• Heavy alcohol consumption is associated with increased risk 6, 5

Medical Conditions

• Pernicious anemia significantly increases risk through its relationship with chronic atrophic gastritis 2
• Previous gastric resection for benign disease increases risk 1
• Chronic atrophic gastritis and intestinal metaplasia are important precursors for malignant transformation 1
• Menetrier's disease (a rare condition with enlarged gastric folds) increases risk 1

Socioeconomic and Geographic Factors

• Geographic variation is substantial, with highest rates in East Asia, South America, and Eastern Europe 1
• Early-generation immigrants from high-incidence regions (Eastern Europe, Andean Latin America, East Asia) have elevated risk 1
• Persistent poverty is associated with 43% higher gastric cancer mortality rates 1
• Obesity is increasingly recognized as a risk factor, particularly for gastric cardia cancer 1, 6

Occupational Exposures

• Foundry workers have increased risk, with dust iron being an important causative factor 6
• Exposure to environmental carcinogens in certain occupations may increase risk 1, 7

Important Clinical Considerations

• Patients with multiple risk factors should be considered for endoscopic screening, especially if they are 45 years or older 1
• H. pylori eradication is the most promising strategy for primary prevention of gastric cancer 2, 3
• Alarm symptoms that warrant prompt investigation include dysphagia, weight loss, anemia, anorexia, and persistent dyspepsia, especially in those over 55 years 1
• A diet high in fruits, vegetables, whole grains, and low in salt may reduce gastric cancer risk 5, 3

Understanding these risk factors is crucial for identifying high-risk individuals who may benefit from screening, surveillance, and preventive interventions to reduce gastric cancer morbidity and mortality.