Tipping the Scale Toward Gastric Disease: A Host-Pathogen Genomic Mismatch?

Purpose of review: Chronic infection with Helicobacter pylori infection is necessary but not sufficient to initiate development of intestinal-type gastric adenocarcinoma. It is not clear what additional factors tip the scale from commensal bacteria towards a pathogen that facilitates development of gastric cancer. Genetic variants in both the pathogen and host have been implicated, but neither alone explains a substantial portion of disease risk.

Recent findings: In this review, we consider studies that address the important role of human and bacterial genetics, ancestry and their interactions in determining gastric disease risk. We observe gaps in the current literature that should guide future work to confirm the hypothesis of the interacting roles of host and bacterial genetics that will be necessary to translate these findings into clinically relevant information.

Summary: We summarize genetic risk factors for gastric disease in both H. pylori and human hosts. However, genetic variation of one or the other organism in isolation insufficiently explains gastric disease risk. The most promising models of gastric disease risk simultaneously consider the genetic variation of both the H. pylori and human host, under a co-evolution model.