Preventing Stomach Cancer: The Link to H. pylori Bacteria

Pathway to Discovery

In 1984, two Australian scientists, Dr. Barry J. Marshall and Dr. J. Robin Warren, discovered a bacteria in patients with gastritis. Going against the prevailing medical thinking of the time, the researchers hypothesized that this bacteria and not psychological stress caused gastritis and ulcers. Although the medical community was skeptical, NCI began supporting studies to test this novel hypothesis. This support included basic research in new animal models that demonstrated that H. pylori infections contribute to gastritis.

NCI researchers now use these animal models to:

• examine modes of infection
• test screening and treatment strategies
• study the immune response to H. pylori infections

Once H. pylori infections were linked to gastritis, researchers began to suspect a connection between the bacteria and stomach cancer. For example, NCI supported a key study that provided the first strong evidence that people infected with H. pylori bacteria are much more likely to be diagnosed with stomach cancer.

The findings from additional studies now suggest that people infected with H. pylori are six times more likely to develop stomach cancer than people not infected. Recent studies of these types of cancers indicate that nearly 90 percent of these cancers are associated with H. pylori infections.

The link between H. pylori infections and stomach cancer was discovered at the same time as the link between viral infections and other types of cancer. This discovery marked a major shift in the way scientists viewed cancer. New cancer treatment and prevention strategies were developed to address these potentially treatable or preventable infections that are at the root of some cancers.

These discoveries also sparked breakthroughs in other types of cancer as scientists began to carefully examine other viral and bacterial connections.

Enhancing Cancer Care

Stomach cancer is the fourth most common cancer worldwide and the second most common cause of cancer death globally. The connection between H. pylori infection and stomach cancer fueled a need for noninvasive screening methods for the bacteria. Through NCI support, numerous screening methods were developed, allowing researchers to screen large numbers of people and gather epidemiological data that will improve our current understanding of stomach cancer worldwide.

The widespread occurrence of H. pylori infections also spurred the development of strategies to eradicate the bacteria, with the overall aim of reducing the occurrence and recurrence of stomach cancer. Early NCI-supported animal studies suggested that antibiotics could be effective.

Building on these findings, NCI supported the Shandong Intervention Trial, which tested a short-term antibiotic treatment for H. pylori infections. The results showed a reduction in the percentage of the participants with precancerous stomach lesions. Follow-up nearly 15 years later showed that the antibiotic treatment significantly reduced the number of new cases of stomach cancer. A similar trend was also seen for reducing deaths caused by stomach cancer.

These results appear to support early treatment strategies to eradicate the H. pylori bacteria. However, using these treatment strategies is challenging. Sometimes H. pylori infections are antibiotic resistant and people can become reinfected. The high cost of extensive antibiotic treatment also may make it impractical to provide it to all patients who have H. pylori infections.

Turning Discovery into Health

H. pylori bacteria affect nearly half of the world's population. Remarkably, only a small percentage of individuals who are infected develop gastritis, ulcers, and stomach cancer. This finding indicates that while having H. pylori may increase a person's chance of having stomach cancer in the future, it is not the sole cause of the disease.

Researchers are now looking for small genetic differences in people that affect the way they fight off bacterial infections. Finding these differences may allow clinicians to limit antibiotic treatment to high-risk patients and reduce the risk of generating strains of H. pylori bacteria that are resistant to treatment.

Researchers are also examining the genetic difference between harmful and harmless versions of bacteria. These studies will help clinicians screen patients for the most dangerous types of H. pylori bacteria. NCI-supported researchers also are working to develop a vaccine to prevent H. pylori infections. The overall goal of this research is to dramatically reduce the number of new cases of stomach cancer.

Research to Practice: NCI's Role

NCI has supported a variety of projects that have helped broaden our understanding of H. pylori and stomach cancer. The non-invasive screening methods developed are integral in monitoring effectiveness of H. pylori eradication strategies and will be essential for identifying people at the highest risk of developing H. pylori mediated stomach cancer. The renowned Cancer Genome Atlas program seeks to find answers to some of these questions by analyzing the genetic variations of stomach cancer.

Another project is the Human Microbiome Project, through which NCI and its partners are supporting the characterization of bacterial species, including H. pylori, within the stomach. This will greatly improve understanding of the complex bacterial interactions that contribute to stomach cancer.

Finally, investigators across NCI have organized the Esophago-Gastric Cancer Task Force, which facilitates quality investigations in gastrointestinal cancer clinical research.

Selected Resources

Lee A, Fox JG, Otto G, Murphy J. A small animal model of human Heliobacter pylori active chronic gastritis. Gastroenterology. 1990;99(5):1315-1323. [PUBMED Abstract]

Ma JL, Zhang L, Brown LM, et al. Fifteen-year effects of Heliobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst. 2012;104(6):488-492. [PUBMED Abstract]

Parsonnet J, Friedman GD, Vandersteen DP, et al. Heliobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127-1131. [PUBMED Abstract]