Foster Dion, Spruill Laura, Walter Katherine R, Nogueira Lourdes M, Fedarovich Hleb, Turner Ryan Y, Ahmed Mahtabuddin, Salley Judith D, Ford Marvella E, Findlay Victoria J, Turner David P
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.
Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, South Carolina.
Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2186-91. doi: 10.1158/1055-9965.EPI-14-0564. Epub 2014 Jul 22.
Socioeconomic and environmental influences are established factors promoting cancer disparity, but the contribution of biologic factors is not clear. We report a mechanistic link between carbohydrate-derived metabolites and cancer that may provide a biologic consequence of established factors of cancer disparity. Glycation is the nonenzymatic glycosylation of carbohydrates to macromolecules, which produces reactive metabolites called advanced glycation end products (AGE). A sedentary lifestyle and poor diet all promote disease and the AGE accumulation pool in our bodies and also increase cancer risk. We examined AGE metabolites in clinical specimens of African American and European American patients with prostate cancer and found a higher AGE concentration in these specimens among African American patients when compared with European American patients. Elevated AGE levels corresponded with expression of the receptor for AGE (RAGE or AGER). We show that AGE-mediated increases in cancer-associated processes are dependent upon RAGE. Aberrant AGE accumulation may represent a metabolic susceptibility difference that contributes to cancer disparity.
社会经济和环境影响是导致癌症差异的既定因素,但生物因素的作用尚不清楚。我们报告了碳水化合物衍生代谢物与癌症之间的一种机制联系,这可能为癌症差异的既定因素提供生物学后果。糖基化是碳水化合物与大分子的非酶糖基化,会产生称为晚期糖基化终产物(AGE)的反应性代谢物。久坐不动的生活方式和不良饮食都会促进疾病发展以及我们体内AGE积累池的增加,同时也会增加患癌风险。我们检测了非裔美国人和欧裔美国人前列腺癌患者临床标本中的AGE代谢物,发现与欧裔美国患者相比,非裔美国患者这些标本中的AGE浓度更高。AGE水平升高与AGE受体(RAGE或AGER)的表达相对应。我们表明,AGE介导的癌症相关过程增加依赖于RAGE。异常的AGE积累可能代表一种代谢易感性差异,它导致了癌症差异。