Helicobacter and gastric cancer disease mechanisms: host response and disease susceptibility.

Helicobacter infection is the single most common cause of gastric cancer worldwide. Although infection prevention and eradication of established infection offer the potential for cure, these strategies are neither feasible nor practical for widespread implementation. Patients most at risk need to be identified and targeted for treatment. For disease to occur, bacterial, environmental, and nutritional factors require a genetically susceptible host. Consequently, it is important to understand how the organism interacts with the host to cause disease. Only through an understanding of what places a patient at risk can we hope to identify susceptible patients early enough in disease to have an impact on their outcome. The immune response is the single most important determinant of disease. Single nucleotide polymorphisms within the promoter region of several critical proinflammatory genes dramatically increase the risk of Helicobacter-associated gastric cancer. Additionally, environmental and dietary factors may modulate the immune response or directly influence key apoptotic and proliferative signaling cascades to alter disease presentation. Lastly, concurrent disease states may have a dramatic impact on the host response to Helicobacter infection and influence disease. An understanding of the immune signaling pathways responsible for disease and the ways in which environmental risk factors influence these pathways will allow identification of populations that are most at risk and targeted prevention and treatment strategies.