Abstract
Gastric cancer (or: stomach cancer) remains a frequent cause of cancer deaths worldwide, but its incidence has plummeted in most countries for several decades. The causes of this unique decrease are presumed to comprise improved hygiene, changes in diet, and reduced prevalence of Helicobacter pylori infection. This chapter first describes the molecular and cellular pathogenesis of the predominant histological subtypes of gastric cancer, the intestinal type, and the diffuse type. The intestinal type develops from gastric atrophy via intestinal metaplasia and dysplasia. Intestinal-type gastric cancers share certain genetic alterations with colon adenocarcinoma, such as mutations enhancing WNT/β-Catenin and disrupting TGFβ signaling. Likewise, a subset of these cancers displays microsatellite instability. Metaplasia is associated with changed expression of transcription factors that regulate intestinal differentiation. Diffuse-type gastric cancers are characterized by highly invasive small groups of loosely adherent cancer cells as a consequence of mutations truncating E-Cadherin or oncogenic mutations activating the small GTP-binding protein RHOA. TP53 inactivation is frequent in both histological types. A second major theme of this chapter are the complex mechanisms by which the biological carcinogen H. pylori causes gastric cancers in some of the many individuals that are infected by the bacterium. The outcome of the infection is determined by genetic variability of the pathogen strains and by the immune response of the host. In the bacterium, variations in pathogenicity genes influence the risk of chronic inflammation, ulcers, and cancer. Furthermore, carcinogenesis by H. pylori is modulated by cofactors, such as carcinogenic and protective ingredients of the diet.
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Notes
- 1.
An early diagnosis program introduced in Japan, a high-incidence country for gastric cancer, looks to become successful in reducing mortality.
- 2.
H. pylori causes in addition a low-malignant lymphoma, mucosa-associated lymphoid tissue (MALT), in an even lower fraction of its hosts, estimated as <0.1%.
- 3.
Similarly high frequencies of CDH1 mutations are found in a few other cancers, especially lobular breast carcinoma and a rare variant of urinary bladder cancer, plasmacytoid urothelial carcinoma.
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Schulz, W.A. (2023). Stomach Cancer. In: Molecular Biology of Human Cancers. Springer, Cham. https://doi.org/10.1007/978-3-031-16286-2_18
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DOI: https://doi.org/10.1007/978-3-031-16286-2_18
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