Mismatched bacterial-host ancestries play key role in gastric cancer
Patients infected with Helicobacter pylori strains derived from different geographical human ancestries than their own are likely to develop more severe symptoms which include gastric cancers, says an expert.
According to Professor Richard Peek, director of the Vanderbilt Digestive Disease Center, USA, the interactions between a host’s genotype, the genetic origins of the infecting H. pylori strain, and the surrounding environment are the main factors influencing the severity of resulting gastric symptoms, rather than any single determinant in isolation.
“H. pylori is the strongest known risk factor for gastric cancer; however, a majority of individuals who are infected do not develop malignancies,” said Peek, also the current editor-in-chief of Gastroenterology.
Infection by H. pylori can often be benign, with no detectable abnormalities on the host’s gut mucosa. However, some patients may experience symptoms ranging from non-atrophic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and to gastric adenocarcinoma at the most extreme.
Speaking at the recent Asia Pacific Digestive Week in Kobe, Japan, Peek highlighted a recent study comparing Columbian populations living in two geographically distinct areas of South America (coastal and mountain), both of which had an approximately 90% prevalence rate of H. pylori infection, but with significantly different incidences of gastric cancer (150 per 100,000 in the mountains, versus 6 per 100,000 at the coast). Analysis of host and bacterial DNA found that severity of gastric damage generally increased when hosts of primarily Amerindian or European ancestry were infected with H. pylori of primarily African ancestry, but were reduced or benign when both host and bacteria were of primarily African ancestry. [PNAS 2013; doi: 10.1073/pnas.1318093111; Front Genet 2014;doi:10.3389/fgene.2014.00290]
Peek added that phylogenetic studies of over 700 H. pylori strains have shown that the species has persisted and intimately co-evolved with migrating groups of humans from the African continent into other regions of the world, with the oldest strains isolated from the intestinal tract of 5,300-year-old mummified human remains. [Science 2016;351;162–165]
“Recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer,” wrote Peek in a recent review, adding that host-microbe genetic interactions could influence the CagA oncoprotein molecular signaling mechanism, which has been shown to activate stem cell-like properties in the epithelial cells beneath the gastric mucosa. [Gastroenterology 2016;150(1):64–78]
Environmental cofactors such as nutrient deficiency and alterations in gut microbiota have also been shown to play a role in the severity of infection; according to Peek, iron depletion has been shown to cause increased H. pylori colonization of the gastric glands and augmented intracellular secretion of Cag proteins, while the presence of certain bacterial species such as Leptotrichia wadei and Veillonella sp. have been linked with increased risk of gastric carcinoma. [Gut 2014;doi:10.1136/gutjnl-2014-307650; Scientific Reports 2016; doi:10.1038/srep18594]