How much does the risk of stomach cancer increase with H. pylori infection?

H. pylori Infection Increases Stomach Cancer Risk by Two to Three Times

H. pylori infection increases the risk of stomach cancer by approximately 2-3 times in infected individuals compared to those without infection. 1 This risk is even higher for specific populations and under certain conditions.

Risk Factors and Mechanisms

Established Risk Increase

• First-degree relatives of gastric cancer patients have a 2-3 fold increased risk of developing gastric cancer 1
• H. pylori infection is responsible for 90% of the global gastric cancer burden 1
• Meta-analyses conclude the risk increase from H. pylori infection is approximately 2.5-fold, particularly for non-cardia cancers 1
• Some studies have assessed the risk as 2-6 fold, depending on specific pathogenic strains 1

Pathophysiological Mechanism

H. pylori causes a cascade of pathological changes that increase cancer risk:

1. Chronic Inflammation: H. pylori causes persistent active gastritis that becomes chronic 1
2. Atrophic Gastritis: Inflammation progresses to atrophy, a precancerous condition 1
3. Intestinal Metaplasia: Further progression leads to intestinal metaplasia, another precancerous condition 1
4. Hypochlorhydria: Atrophic corpus gastritis causes reduced stomach acid 1
5. Bacterial Overgrowth: Low acid allows overgrowth of non-H. pylori organisms that produce carcinogenic metabolites 1
6. Reduced Antioxidants: H. pylori infection decreases protective ascorbic acid in the stomach 1

Risk Modifiers

The risk of gastric cancer with H. pylori infection varies based on:

• Strain Virulence: CagA-positive H. pylori strains increase noncardia gastric cancer risk by 18.2-fold compared to 5.2-fold with CagA-negative strains 2
• Gastric Atrophy Severity: In CagA-positive infections, mild/moderate atrophy increases risk 6.4-fold, while severe atrophy increases risk 11.8-fold 2
• Anatomical Location: Risk is higher for non-cardia cancers than for cardia cancers 1
• Family History: Having multiple first-degree relatives with gastric cancer increases risk by a factor of 10 1

Prevention Through Eradication

H. pylori eradication significantly reduces gastric cancer risk:

• Meta-analyses of RCTs show H. pylori eradication is associated with a 46% reduction in gastric cancer incidence 1
• The greatest benefit occurs when eradication is performed before the development of precancerous changes 1
• Even after successful eradication, there remains a 0.30% annual risk of developing gastric cancer 3
• Both intestinal (0.17% per year) and diffuse (0.13% per year) types of gastric cancer can develop even after successful eradication 3

Clinical Implications

• Screening: Consider H. pylori screening in high-risk individuals (Asian, Hispanic, and Black Americans) 1
• Family Testing: Consider "familial-based testing" for adult household members of H. pylori-positive individuals 1
• Eradication: H. pylori eradication is essential for gastric cancer prevention 1
• Surveillance: Patients with precancerous conditions (atrophic gastritis, intestinal metaplasia) require endoscopic surveillance even after H. pylori eradication 1

Common Pitfalls

• Failing to recognize that H. pylori eradication does not eliminate cancer risk completely
• Overlooking the need for surveillance in patients with precancerous conditions
• Not considering family-based testing when H. pylori is detected in an individual
• Ignoring the higher risk associated with CagA-positive strains

H. pylori infection is the most consistent risk factor for gastric cancer, and its elimination is the most promising strategy to reduce gastric cancer incidence 1. However, ongoing surveillance is necessary for those with established precancerous changes.