Chronic inflammation and cancer: potential role of Bcl-2 gene family members as regulators of cellular antioxidant status

The incidence of cancer is increased in all gastrointestinal (GI) tissues as a result of chronic inflammation. These cancers may develop in cells that are selected for resistance to inflammatory products by virtue of overexpressing the antioxidant protein Bcl-2 or other Bcl-2 gene family members that have antioxidant activity. Unfortunately, Bcl-2 also functions as an anti-apoptotic. Bcl-2 overexpression can increase cellular lifetime and increase the likelihood that other cancer-related mutations will accumulate in individual cells. Thus, Bcl-2 expression is cytoprotective, but its expression also increases the risk of cancer incidence. This is perhaps more evident in the GI tract, which is exposed to more potential mutagens relative to other tissues.