Cellular response to bacteria may explain why infection sometimes causes stomach cancer
Researchers have uncovered a promising clue as to why some people with Helicobacter pylori (H. pylori) infections may be more likely to develop stomach cancer: they may carry a genetic variation that causes cells in the stomach to respond more strongly to the bacteria.
About one-third of the U.S. population—and more than half of the world’s population—is infected with H. pylori, a species of bacteria that can cause gastritis, a type of chronic inflammation in the stomach. In the United States, the rate of H. pylori infection is higher in immigrants from areas where the infection is more common, such as in Asia and Central or South America. Most people with gastritis do not have symptoms, but the lingering inflammation could eventually produce ulcers and other changes to the stomach wall. In fact, infection with H. pylori is the leading known cause of stomach cancer, a disease with a typically poor prognosis because it is usually discovered in its late stages when it is difficult to treat. It is unclear, however, why H. pylori infections are more likely to cause stomach cancer in some people but not others.
Researchers sought to answer this question by examining how cells in the stomach interact with the Helicobacter bacteria during an infection. In a laboratory model that used cultured cells from mice or humans, they found that cells from the stomach responded to the infection by producing a chemical called interferon alpha (IFNα). This chemical signal was found to then convert nearby immune cells into “immune suppressor cells,” which could potentially dampen the stomach’s immune response and create an environment that is favorable for cancer development and growth. Using a mouse model of Helicobacter-induced stomach cancer, the researchers showed that blocking IFNα prevented the formation of these immune suppressor cells and the cells that are the precursors to stomach cancer. The researchers also looked at samples from almost 200 men and women in China and Vietnam with gastritis (with or without H. pylori) and found that some people had a variation in a gene involved in the cellular response to H. pylori infections. If the people with this genetic variant also harbored H. pylori, their stomachs had higher levels of IFNα, more immune suppressor cells, and a higher incidence of cancer than those with a more common genetic variant.
These studies provide a possible reason why some people with H. pylori infections are more likely to develop stomach cancer: they have a genetic variation that causes a more robust response to the infection, leading to a stronger suppression of the local immune response that typically keeps cancer cells in check. This finding suggests that people who have this genetic variation may benefit from more clinical surveillance to detect the disease early, when it is more likely to respond to treatment.
Ding L, Chakrabarti J, Sheriff S, …Merchant JL. Toll-like receptor 9 pathway mediates Schlafen+-MDSC polarization during Helicobacter-induced gastric metaplasias. Gastroenterology 163: 411-425, 2022.