Possible involvement of tobacco-derived advanced glycation end products (AGEs) in an increased risk for developing cancers and cardiovascular disease in former smokers.

Tobacco smoking is one of the strongest risk factors for various disorders such as lung cancers and cardiovascular disease (CVD). Further, former smokers remain at an increased risk for developing lung cancers and CVD even years after they stop smoking. These observation suggest that expression levels of some of the genes related to tobacco smoking may not return to levels similar to never smokers and could be permanently altered despite prolonged smoking cessation, thereby being involved in the development of lung cancers and CVD. The modification, aggregation, and deposition of proteins are a prominent part of many pathological processes and can play a direct role in tissue damage. Advanced glycation end products (AGEs) have been shown to play a role in the development of many of the pathological sequelae of aging and diabetes such as CVD and cancer growth and metastasis. Moreover, there are several papers to show that tobacco smoke is a source of toxic reactive glycation products. Further, recent epidemiological and prospective data have supported the concept of 'metabolic memory', a long-term influence of previous hyperglycemia on the development of CVD in diabetes. Potential mechanism for propagating this 'memory' is considered to be the non-enzymatic glycation of proteins because the process of formation and accumulation of AGEs are most compatible with the theory. Therefore, it is conceivable that tobacco-derived AGEs are also involved in the increased risk for developing cancers and CVD in former smokers. In this paper, we would like to propose the possible ways of testing our hypotheses. Are tissue levels of AGEs still higher in former smokers, compared with age-, sex- and other confounders-matched non-smokers? If the answer is yes, are the tissue levels of AGEs following smoking cessation decreased? If we examine the effects of smoking cessation as a function of years since quitting, is the extent of decrease in tissue AGEs levels parallel to that of risk reduction for developing cancers and CVD? Further, are genes that are permanently altered despite prolonged smoking cessation identical to those that regulated by AGEs? These investigations could clarify whether tobacco-derived AGEs are involved in sustained tissue injury in former smokers.