National Cancer Institute

What is Helicobacter pylori?

Helicobacter pylori, or H. pylori, is a spiral-shaped bacterium that grows in the mucus layer that coats the inside of the human stomach.

To survive in the harsh, acidic environment of the stomach, H. pylori secretes an enzyme called urease, which converts the chemical urea to ammonia. The production of ammonia around H. pylori neutralizes the acidity of the stomach, making it more hospitable for the bacterium. In addition, the helical shape of H. pylori allows it to burrow into the mucus layer, which is less acidic than the inside space, or lumen, of the stomach. H. pylori can also attach to the cells that line the inner surface of the stomach.

Although immune cells that normally recognize and attack invading bacteria accumulate near sites of H. pylori infection, they are unable to reach the stomach lining. In addition, H. pylori has developed ways of interfering with local immune responses, making them ineffective in eliminating the bacteria (1, 2).

H. pylori has coexisted with humans for many thousands of years and infection with the bacterium is common. The Centers for Disease Control and Prevention (CDC) estimates that approximately two-thirds of the world’s population harbors the bacterium, with infection rates much higher in developing countries than in developed nations.

Although H. pylori infection does not cause illness in most infected people, it is a major risk factor for peptic ulcer disease and is responsible for the majority of ulcers of the stomach and upper small intestine. The National Institute of Diabetes and Digestive and Kidney Diseases ¹ has more information about H. pylori and peptic ulcer disease. 

In 1994, the International Agency for Research on Cancer classified H. pylori as a carcinogen, or cancer-causing agent, in humans, despite conflicting results at the time. Since then, colonization of the stomach with H. pylori has been increasingly accepted as an important cause of stomach cancer and of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (see Questions 2–7). Infection with the bacteria is also associated with a reduced risk of esophageal adenocarcinoma (see Questions 6–8).

Spread of H. pylori is thought to occur through contaminated food and water or through direct mouth-to-mouth contact. In most populations, the bacterium is first acquired during childhood. Children living in crowded conditions and with a lower socioeconomic status are more likely to become infected.

What is gastric cancer?

Gastric cancer, or cancer of the stomach, was once considered a single entity. Now, scientists divide this cancer into two main classes: gastric cardia cancer (cancer of the top inch of the stomach, where it meets the esophagus) and non-cardia gastric cancer (cancer in all other areas of the stomach).

In each of the last 5 years in the United States, approximately 21,000 new cases of gastric cancer were diagnosed and more than 10,000 deaths were caused by the disease. Gastric cancer is the second most common cause of cancer-related deaths in the world, killing approximately 738,000 people in 2008 (3). Gastric cancer is less common in the United States and other Western countries than in countries in Asia and South America.

Overall, gastric cancer incidence rates are decreasing. However, this decline is mainly in the rates of non-cardia gastric cancer (4). Gastric cardia cancer, which was once very uncommon, now constitutes nearly half of all stomach cancers among white males in the United States.

Infection with H. pylori is the primary identified cause of gastric cancer. Other factors that increase the risk for gastric cancer include chronic gastritis; older age; male sex; a diet high in salted, smoked, or poorly preserved foods and low in fruits and vegetables; tobacco smoking; pernicious anemia; a history of stomach surgery for benign conditions; and a family history of stomach cancer (5, 6).

What evidence shows that H. pylori infection causes gastric cancer?

Epidemiology studies have shown that individuals infected with H. pylori have an increased risk of gastric adenocarcinoma (1, 2, 7–11). In 2001, a combined analysis of 12 studies of H. pylori and gastric cancer estimated that the risk of adenocarcinoma in non-cardia regions of the stomach was nearly six times higher for H. pylori-infected people than for uninfected people (7).

Evidence for an association comes mainly from prospective cohort studies such as the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study in Finland, which involved nearly 30,000 male smokers who were aged 50 to 69 years at study enrollment. This study was designed to determine whether daily supplementation with alpha-tocopherol, beta-carotene, or both would reduce the number of lung or other cancers (12). H. pylori infection status was determined by analyzing blood samples obtained from each study participant at the time of enrollment in the study to see if they contained antibodies to the bacterium. Participants were enrolled during 1985 through 1988 and followed through 1999. Comparing subjects who developed gastric cancer with noncancer control subjects, the researchers found that H. pylori-infected individuals had a nearly eightfold increased risk for non-cardia gastric cancer (13).

Can treatment to eradicate H. pylori infection reduce gastric cancer rates?

Only two clinical trials have been conducted to determine whether eradicating H. pylori infection with antimicrobial therapy will reduce the incidence of gastric cancer. The total number of gastric cancers that developed in these studies was too small to make definitive statements. However, a meta-analysis of six randomized trials suggested that eradication may lead to a modest reduction in gastric cancer risk, because study participants were less likely to have precancerous lesions worsen if their H. pylori infections were eliminated (14).

What is gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and what is the evidence that it can be caused by H. pylori infection?

Gastric MALT lymphoma is a rare type of non-Hodgkin lymphoma that is characterized by the slow multiplication of B lymphocytes, a type of immune cell, in the stomach lining. This cancer represents approximately 12 percent of the extranodal (outside of lymph nodes) non-Hodgkin lymphoma that occurs among men and approximately 18 percent of extranodal non-Hodgkin lymphoma among women (15). During the period 1999–2003, the annual incidence of gastric MALT lymphoma in the United States was about one case for every 100,000 persons in the population.

Normally, the lining of the stomach lacks lymphoid (immune system) tissue, but development of this tissue is often stimulated in response to colonization of the lining by H. pylori (2). Only in rare cases does this tissue give rise to MALT lymphoma. However, nearly all patients with gastric MALT lymphoma show signs of H. pylori infection, and the risk of developing this tumor is more than six times higher in infected people than in uninfected people (16, 17).

What is the evidence that H. pylori infection may reduce the risk of some cancers?

The ATBC cohort study revealed that the risk of gastric cardia cancer among H. pylori-infected individuals was about one-third of that among uninfected individuals (13). Several other studies have also detected an inverse relationship between H. pylori infection and gastric cardia cancer (18–20), although the evidence is not entirely consistent (21). The possibility of an inverse relationship between the bacterium and gastric cardia cancer is supported by the corresponding decrease in H. pylori infection rates in Western countries during the past century—the result of improved hygiene and widespread antibiotic use—and the increase in rates of gastric cardia cancer in these same regions.

Similar epidemiologic evidence suggests that H. pylori infection may be associated with a lower risk of esophageal adenocarcinoma. For example, a large case-control study in Sweden showed that the risk of esophageal adenocarcinoma in H. pylori-infected individuals was one-third that of uninfected individuals (20). A meta-analysis of 13 studies, including the Swedish study, found a 45 percent reduction in risk of esophageal adenocarcinoma with H. pylori infection (22). Moreover, as with gastric cardia cancer, dramatic increases in esophageal adenocarcinoma rates in several Western countries parallel the declines in H. pylori infection rates.

How might H. pylori infection decrease the risk of some cancers while increasing the risk of other cancers?

Although it is not known for certain how H. pylori infection increases the risk of gastric cancer, some researchers speculate that the long-term presence of an inflammatory response predisposes cells in the stomach lining to become cancerous. This idea is supported by the finding that increased expression of a single cytokine (interleukin-1-beta) in the stomach of transgenic mice causes sporadic gastric inflammation and cancer (23). The increased cell turnover resulting from ongoing cellular damage could increase the likelihood that cells will develop harmful mutations.

One hypothesis that may explain reduced risks of gastric cardia and esophageal adenocarcinoma in H. pylori-infected individuals relates to the decline in stomach acidity that is often seen after decades of H. pylori colonization. This decline would reduce acid reflux into the esophagus, a major risk factor for adenocarcinomas affecting the upper stomach and esophagus.

What is cagA-positive H. pylori and how does it affect the risk of gastric and esophageal cancers?

Some H. pylori bacteria use a needle-like appendage to inject a toxin produced by a gene called cytotoxin-associated gene A (cagA) into the junctions where cells of the stomach lining meet (24, 25). This toxin (known as CagA) alters the structure of stomach cells and allows the bacteria to attach to them more easily. Long-term exposure to the toxin causes chronic inflammation. However, not all strains of H. pylori carry the cagA gene; those that do are classified as cagA-positive.

Epidemiologic evidence suggests that infection with cagA-positive strains is especially associated with an increased risk of non-cardia gastric cancer and with reduced risks of gastric cardia cancer and esophageal adenocarcinoma. For example, a meta-analysis of 16 case-control studies conducted around the world showed that individuals infected with cagA-positive H. pylori had twice the risk of non-cardia gastric cancer than individuals infected with cagA-negative H. pylori (26). Conversely, a case-control study conducted in Sweden found that people infected with cagA-positive H. pylori had a statistically significantly reduced risk of esophageal adenocarcinoma (20). Similarly, another case-control study conducted in the United States found that infection with cagA-positive H. pylori was associated with a reduced risk of esophageal adenocarcinoma and gastric cardia cancer combined, but that infection with cagA-negative strains was not associated with risk (27).

Recent research has suggested a potential mechanism by which CagA could contribute to gastric carcinogenesis. In three studies, infection with CagA-positive H. pylori was associated with inactivation of tumor suppressor proteins, including p53 (28–30).

Is H. pylori infection associated with any other cancer?

A possible association between H. pylori infection and pancreatic cancer was suggested by several small epidemiology studies that found an increased risk of pancreatic cancer among patients who had been treated with surgery for peptic ulcer disease up to 20 years earlier. Furthermore, in the ATBC cohort study, individuals infected with H. pylori at the time of study enrollment were approximately twice as likely to develop pancreatic cancer as those without the infection (31).

However, this association between H. pylori infection and pancreatic cancer was not confirmed in another study that involved 128,992 adults. When the participants who developed pancreatic cancer were compared with control subjects, no evidence was found that individuals infected with H. pylori at study enrollment were more likely to develop pancreatic cancer than those who were not infected (32).

The relationship between H. pylori and colorectal cancer has also been studied. In a nested case-control study of men in the ATBC cancer prevention clinical trial, researchers found no evidence of H. pylori being a risk factor for colorectal adenocarcinoma (33).

Who should seek diagnosis and treatment of an H. pylori infection?

According to the CDC ², people who have active gastric or duodenal ulcers or a documented history of ulcers should be tested for H. pylori, and, if they are infected, should be treated. Testing for and treating H. pylori infection is also recommended after resection of early gastric cancer and for low-grade gastric MALT lymphoma. However, most experts agree that the available evidence does not support widespread testing for and eradication of H. pylori infection (34).