Inflammation, atrophy, and gastric cancer

Abstract

The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world's population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment.

Interleukin-4 and -8 Gene Polymorphisms and Risk of Gastric Cancer in a Population in Southwestern China

“…The association between inflammation and cancer is well established, and in particular GC is a prime example, in which HP infection induces chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and malignancy (Fox et al, 2007).…”

Osteopontin depletion decreases inflammation and gastric epithelial proliferation during Helicobacter pylori infection in mice

“…1,2 HP-infected gastric mucosa progresses through stages of chronic gastritis, glandular atrophy, intestinal metaplasia, dysplasia, and gastric cancer. 3 HP produce a variety of virulence factors such as CagA and VacA that can affect host intracellular signaling pathways and play an important role in determining the outcome of HP infection. 3 However, they are not absolute determinants of clinical outcomes because most individuals remain asymptomatic after HP infection.…”

“…3 HP produce a variety of virulence factors such as CagA and VacA that can affect host intracellular signaling pathways and play an important role in determining the outcome of HP infection. 3 However, they are not absolute determinants of clinical outcomes because most individuals remain asymptomatic after HP infection. 4 The variable outcomes of HP infection can be attributed to inflammatory responses governed by host factors as well as HP virulence factors.…”

“…4 HP-induced chronic inflammation induces DNA alterations and imbalanced epithelial cell turnover, providing opportunities for mitotic error that could ultimately contribute to the development of gastric cancer. 3,[6][7][8] Infiltrating macrophages, in particular, produce various cytokines and growth factors such as IL-1β that could attract more inflammatory cells and induces the proliferation of gastric epithelial cells. 9,10 A recent study demonstrated that IL-1β physiologically induced by HP infection enhanced gastric inflammation and the number of gastric tumors using Il1b-mull mice.…”

Late reactivation of sonic hedgehog by Helicobacter pylori results in population of gastric epithelial cells that are resistant to apoptosis: Implication for gastric carcinogenesis

“…Therefore, it is suggested that increased cell proliferation in gastric epithelium in vivo might be an indirect or secondary response to H. pylori infection [43][44][45]. Together with the previous publications that suppressed apoptosis might be one of major pathogenic factors in H. pylori-associated carcinogenesis [46][47][48] and oncogenic stem cells contributed to H. pylori-associated carcinogenesis [49], we could conclude that the reemergence of Shh expressing cells can explain these compensatory or counteractive privileges of proliferation through imbalanced epithelial turnover and this anti-apoptotic steps and proliferative privileges through Shh reactivation could be the necessary path for H. pylori-associated carcinogenesis. Even though we found the possible role of switching expression of Shh during the progression of gastric diseases after H. pylori infection, more documentation to define the role of Shh expression in H. pylori gastric carcinogenesis, especially progression from adenoma to carcinoma will be required to draw the definite conclusion.…”