Chronic gastritis increases cancer risk in older adults primarily by creating a persistent inflammatory environment in the stomach lining that gradually damages the tissue and leads to a series of precancerous changes. This process often begins with chronic inflammation caused by factors such as Helicobacter pylori infection or autoimmune reactions, which over time can transform normal stomach cells into abnormal ones that are more likely to become cancerous.
At the core of this risk is the ongoing inflammation in the gastric mucosa, the stomach’s inner lining. When the stomach lining is chronically inflamed, immune cells continuously release substances like cytokines and reactive oxygen species that damage DNA and disrupt normal cell functions. This persistent injury and repair cycle can cause the stomach lining to thin (atrophy), lose its normal structure, and undergo abnormal changes such as intestinal metaplasia, where stomach cells start resembling intestinal cells. These changes create a fertile ground for genetic mutations and cellular dysplasia, which are precursors to gastric cancer.
One of the most common causes of chronic gastritis is infection with Helicobacter pylori, a bacterium that colonizes the stomach lining. H. pylori produces virulence factors such as CagA and VacA proteins that directly interfere with the stomach cells’ normal signaling pathways and immune responses. The CagA protein, for example, can enter gastric epithelial cells and activate inflammatory pathways like NF-kappa B, leading to the secretion of pro-inflammatory cytokines such as interleukin-8 and tumor necrosis factor-alpha. This sustained inflammatory response not only damages the cells but also weakens the stomach’s protective barriers, making it more vulnerable to further injury and carcinogenic influences.
As the infection persists, the stomach lining undergoes a stepwise progression: from chronic non-atrophic gastritis to atrophic gastritis (where the glands that produce acid and digestive enzymes are lost), then to intestinal metaplasia, dysplasia, and eventually gastric adenocarcinoma, a type of stomach cancer. This sequence is often referred to as the Correa cascade. The risk of cancer increases especially when the inflammation leads to atrophy and intestinal metaplasia, which are considered precancerous conditions.
In older adults, the risk is heightened because the cumulative effects of chronic inflammation and tissue damage have had more time to accumulate. Aging also impairs the immune system’s ability to clear infections and repair damaged tissues effectively, allowing the inflammatory process to persist unchecked. Additionally, older adults may have other risk factors such as genetic predispositions, dietary habits, or coexisting conditions that further promote carcinogenesis.
Autoimmune gastritis, another form of chronic gastritis, also increases cancer risk by a similar mechanism but through an immune attack on the stomach’s acid-producing cells rather than infection. This leads to atrophy and metaplasia as well, and although the exact cancer risk varies, it is recognized as a significant factor in gastric carcinogenesis.
Besides inflammation and cellular changes, chronic gastritis can alter the stomach’s environment in ways that promote cancer. For example, reduced acid secretion due to gland loss allows the growth of bacteria that convert dietary nitrates into carcinogenic nitrites. This chemical environment further damages DNA and promotes malignant transformation.
In summary, chronic gastritis increases cancer risk in older adults by sustaining a damaging inflammatory milieu that drives a cascade of cellular and molecular changes in the stomach lining. These changes include atrophy, metaplasia, and dysplasia, which set the stage for the development of gastric cancer. The interplay of persistent infection or autoimmune attack, impaired tissue repair, genetic susceptibility, and environmental factors all contribute to this increased risk over time.
