South America's Hidden Epidemic

Richard Arboleda. Test subject. A Colombian boy gets a breath test for H. pylori.

The Spanish Conquest brought smallpox and measles epidemics that decimated the peoples of the New World. But another pathogen arrived with the colonists, the bacterium called Helicobacter pylori, and new research may explain why it has quietly wreaked havoc in the stomachs of some in the Americas ever since.

More than half of all humans carry H. pylori, and the microbe seems to protect against childhood asthma and esophageal cancer. Yet it causes stomach ulcers and is responsible for 80% to 90% of all stomach cancers, making it the world's second leading cause of cancer mortality, after tobacco. Not everyone harboring the microbe develops stomach cancer, however; in certain parts of the world—much of Africa, for example—such cancers are rare even though many people harbor H. pylori. Microbiologists call this “the African enigma.”

So, why are some hit much harder than others by H. pylori? A group led by researchers at Vanderbilt University in Nashville has been exploring that question in Colombia. The team had previously found that stomach cancer rates in Túquerres, a mountain town in the Andes, were about 150/100,000, compared with 6/100,000 in Tumaco, a coastal city.

In the new study, the team conducted genetic analyses of 121 people from each town who had sought medical attention for stomach pain. The study confirmed that the DNA of the coastal people was largely of African origin; the mountain group, on the other hand, was on average two-thirds Amerindian and a third European, with small traces of African DNA.

The researchers also examined the DNA of the H. pylori specimens collected from the 242 individuals. The bacterium, which has colonized humans for more than 60,000 years, has evolved into distinct strains reflecting its history, such as whether it came from Europe or Africa. Both coastal and mountain groups were colonized with H. pylori strains that had DNA segments of both African and European origin.

Whether they lived in the mountains or the coast, the people of Amerindian descent carrying largely African strains of H. pylori were five times more likely to have gastric cancer or precancerous lesions than were people of largely African descent who carried similar strains, the group reports online today in the Proceedings of the National Academy of Sciences.

Scientists had not previously examined the role that coevolution of host and organism might play in the H. pylori-connected stomach cancer. “We looked at both the bug and the people infected with it,” says study co-author Barbara Schneider, a Vanderbilt molecular biologist. “It turns out that African ancestry in H. pylori strains, combined with Native American ancestry in humans, is a bad combination.”

Those in Tumaco, however, may enjoy their relative protection against stomach cancer because their African ancestors, on the other hand, apparently coevolved with their strains of H. pylori in ways that minimized the carcinogenic effects.

The researchers don't know why people of Amerindian descent are more susceptible to the African H. pylori sequences. Some H. pylori strains contain a set of genes that create a needlelike structure that deposits a cancerous protein called CagA into human cells. These strains are especially carcinogenic. In the Vanderbilt study, however, the impact of combined Amerindian host ancestry and African H. pylori ancestry was five times stronger than that of being infected with a strain that has the CagA-associated genes. One H. pylori interaction may be with diet. The coastal people eat more fresh fruits and vegetables and fish than the more cancer-prone residents of the Andes.

The findings could help fight stomach cancer by offering a way to determine who is at risk from H. pylori infection. More at-risk people could be treated with antibiotics or monitored for gastric lesions that may lead to cancer.

“H. pylori is mostly harmless but it can be deadly,” says infectious disease specialist Jay Solnick of the University of California, Davis, who was not involved in the research. “We've been looking for many years for biomarkers of who should be treated or screened intensively. This could help.”

ORIGINAL: Science Magazine
13 January 2014