AGE-RAGE System and Carcinogenesis

Recent clinical studies have reported an increased risk for various types of cancers in patients with diabetes. Diabetes is characterized by increased oxidative stress conditions. Hyperglycemia induces oxidative stress generation in a variety of cells via various metabolic pathways, thus causing oxidative DNA damage, an initial step of carcinogenesis. There is accumulating evidence that advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate under normal aging process and diabetes, are involved in the development and progression of cancers. AGE stimulate oxidative stress generation through the interaction with a receptor for AGE (RAGE), while oxidative stress generation promotes the formation of AGE and increases the expression of RAGE. These findings suggest that the crosstalk between the AGE-RAGE system and oxidative stress generation may form a positive feedback loop, thus further increasing the risk for cancers in patients with diabetes. This paper reviews current knowledge about the role of AGE-RAGE system in the development of various types of cancers.