Yamagishi S, Matsui T, Nakamura K
Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Med Hypotheses. 2008 Aug;71(2):259-61. doi: 10.1016/j.mehy.2008.03.020. Epub 2008 Apr 29.
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.
吸烟是导致多种疾病（如肺癌和心血管疾病（CVD））的最强风险因素之一。此外，即使戒烟数年，既往吸烟者患肺癌和CVD的风险仍然较高。这些观察结果表明，一些与吸烟相关的基因的表达水平可能不会恢复到与从不吸烟者相似的水平，并且尽管长期戒烟，这些基因的表达水平可能会被永久改变，从而参与肺癌和CVD的发生发展。蛋白质的修饰、聚集和沉积是许多病理过程的重要组成部分，并且可在组织损伤中起直接作用。晚期糖基化终末产物（AGEs）已被证明在许多衰老和糖尿病的病理后遗症（如CVD和癌症生长及转移）的发生发展中起作用。此外，有几篇论文表明烟草烟雾是有毒反应性糖基化产物的一个来源。此外，最近的流行病学和前瞻性数据支持了“代谢记忆”的概念，即既往高血糖对糖尿病患者CVD发生发展的长期影响。传播这种“记忆”的潜在机制被认为是蛋白质的非酶糖基化，因为AGEs的形成和积累过程与该理论最为相符。因此，可以想象，烟草衍生的AGEs也与既往吸烟者发生癌症和CVD的风险增加有关。在本文中，我们想提出检验我们假设的可能方法。与年龄、性别和其他混杂因素相匹配的非吸烟者相比，既往吸烟者体内AGEs的组织水平是否仍然较高？如果答案是肯定的，那么戒烟后组织中AGEs的水平是否会降低？如果我们将戒烟的影响作为戒烟年限的函数进行研究，组织中AGEs水平的下降程度是否与癌症和CVD发生风险的降低程度平行？此外，尽管长期戒烟仍被永久改变的基因是否与受AGEs调节的基因相同？这些研究可以阐明烟草衍生的AGEs是否参与了既往吸烟者的持续组织损伤。
