Helicobacter pylori infection, host genetics and gastric cancer.
Helicobacter pylori infects half the world's population and is responsible for a considerable global health burden, including peptic ulcer disease and gastric cancer. The infection causes a chronic gastritis, the severity and distribution of which determine the clinical outcome. Bacterial, environmental and host genetic factors combine to define the degree of gastric damage. Most patients have a limited mild pan-gastritis with no significant clinical consequences. Antral-predominant gastritis is associated with high gastric acid output and an increased risk of duodenal ulcers. Corpus-predominant gastritis is associated with a reduction in gastric acid, multifocal gastric atrophy and an increased risk of gastric cancer. Host genetic factors are particularly important in defining the severity and extent of Helicobacter-induced gastritis. The most relevant and consistent genetic factors uncovered thus far are in the interleukin-1 and tumor necrosis factor-A gene clusters. These cytokines appear to play a key role in the pathophysiology of gastric cancer and their roles have been confirmed in animal models that mimic human gastric neoplasia. More genetic factors have also been uncovered and, with advancing technology, there is every prospect of defining a full genetic risk profile in the next decade. This will aid in targeting the testing and treatment of Helicobacter pylori, which offers a true opportunity to prevent and defeat this global killer.
Shanks
Anne-Marie
AM
Division of Applied Medicine, Institute of Medical Sciences, School of Medicine and Dentistry, Aberdeen University, Aberdeen, UK.
El-Omar
Emad M
EM
D005756:Gastritis / Q000235:genetics / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D010437:Peptic Ulcer / Q000235:genetics* / Q000382:microbiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D037521:Virulence Factors
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors