How H. pylori Infection Increases Gastric Cancer Risk
Exploring the complex relationship between infection and cancer development
Deep within the human stomach, a spiral-shaped bacterium called Helicobacter pylori (H. pylori) has quietly coexisted with humans for tens of thousands of years. This remarkable microorganism survives in one of the most hostile environments in our body—the acidic stomach—where it has learned to thrive undetected in most cases. Yet, this seemingly peaceful coexistence comes at a cost: H. pylori is recognized as the primary risk factor for gastric cancer, the fifth most common cancer and fourth leading cause of cancer-related deaths worldwide 79.
H. pylori infects approximately 50% of the world's population, but only 1-3% of infected individuals develop gastric cancer.
The discovery of H. pylori earned Barry Marshall and Robin Warren the 2005 Nobel Prize in Physiology or Medicine.
For most of the 20th century, the medical community believed the stomach was a sterile environment where no bacteria could survive due to its extreme acidity. Stress and lifestyle factors were blamed for gastritis and peptic ulcers, with treatments focusing on antacids and diet modification. This prevailing view was dramatically overturned in 1982 when Australian scientists Barry Marshall and Robin Warren made a groundbreaking discovery 26.
Perhaps most remarkably, Marshall provided proof of causality by deliberately drinking a culture of H. pylori and developing severe gastritis, which was then cured by antibiotics—fulfilling Koch's postulates for this bacterium 6. This courageous act challenged medical dogma and revolutionized our understanding of gastric diseases.
Just a decade after Marshall and Warren's discovery, in 1994, the International Agency for Research on Cancer (IARC), part of the World Health Organization, classified H. pylori as a Group 1 carcinogen—the highest risk category reserved for substances known to cause cancer in humans 67.
H. pylori is perhaps the most successful human pathogen, infecting approximately 50% of the world's population—about 4.4 billion people 26. Infection is typically acquired in childhood, especially in developing countries where prevalence can reach 90% 2.
Recent research has projected the future burden of gastric cancer among individuals born between 2008 and 2017. Without effective interventions, this cohort is expected to develop 15.6 million lifetime gastric cancer cases globally, with 76% of these cases (approximately 11.9 million) attributable to H. pylori infection 1.
Initial inflammation of the stomach lining
Thinning of the stomach lining due to long-term inflammation
Transformation of stomach cells to resemble intestinal cells
Appearance of abnormal, precancerous cells
Development of invasive gastric cancer
Interestingly, the relationship between H. pylori infection and gastric cancer risk varies geographically in ways that continue to puzzle scientists. The so-called "African enigma" describes the observation that despite high H. pylori prevalence in Africa, gastric cancer incidence remains relatively low 2.
One of the most compelling pieces of evidence supporting H. pylori eradication for gastric cancer prevention comes from a randomized controlled trial conducted in Shandong, China—an area with exceptionally high gastric cancer rates 4.
This prospective study, which began in July 1994, enrolled 1,630 asymptomatic, H. pylori-positive individuals who were randomly assigned to either receive standard triple therapy for H. pylori eradication or a placebo. Participants were followed for an impressive 26.5 years—until December 2020.
Smokers have approximately a 1.5-fold increased risk
Heavy alcohol consumption increases risk
Reduce salt-preserved foods; increase fruits and vegetables
Obesity increases risk of gastric cardia cancer
A meta-analysis of 11 randomized controlled trials with 104,786 individuals found that eradication therapy significantly reduced gastric cancer risk by 39% (relative risk [RR]: 0.61; 95% CI: 0.47–0.79) 5. The protective effect was even more pronounced in individuals who had undergone endoscopic mucosal resection for early gastric lesions (RR: 0.51; 95% CI: 0.36–0.71) 5.
Studying H. pylori's effects on cancer immunotherapy response
How H. pylori influences gastric epithelial stem cells
Understanding how infection alters gene expression patterns
The story of H. pylori and gastric cancer represents both a challenge and an opportunity for global health. On one hand, gastric cancer remains a devastating disease that claims approximately 768,000 lives annually worldwide 9. On the other hand, we have identified a major preventable cause and have effective tools to address it.
As stated by Lynch, "The whole process of stomach cancer risk associated with H. pylori is one of inflammation" 10. This inflammation, sustained over decades, creates an environment where genetic errors accumulate and eventually lead to cancer.
While research continues to refine our understanding, the current evidence strongly supports the strategic use of H. pylori eradication to reduce gastric cancer burden, particularly in high-risk populations. As we look to the future, integrating this knowledge with emerging technologies like vaccination and personalized risk assessment based on bacterial and host genetics offers hope for substantially reducing the global impact of this devastating cancer.