Abstract PR11: The molecular implications of lifestyle associated metabolites (AGEs) to prostate cancer disparity
Authors: Smith Danzell , Foster Dion , Spruill Laura , Nogueira Lourdes , Krisanits Bradley , Cramer Scott , Ford Marvella , Savage Stephen , Keane Thomas , Findlay Victoria , Turner David 
Published: March 2017

Poor diet, low income, obesity, and a lack of exercise are established lifestyle factors that are known to increase cancer burden and are often more prevalent in African American communities. As our understanding of tumor biology advances, it is becoming increasingly clear that these inter-related lifestyle factors have distinct molecular consequences on the biologic make up of tumors, altering cell signaling events and gene expression profiles to contribute to cancer disparity outcomes such as its earlier development or its progression to more aggressive disease.

Advanced glycation end-products (AGEs), are reactive metabolites produced endogenously as a consequence of glucose uptake during glycolysis. AGEs accumulate in tissues and organs as we grow older to promote multiple chronic disease phenotypes. AGE pathogenic effects are mediated through modification of protein function, genetic fidelity, stress responses and cellular signaling pathways. Critically, cancer disparity factors such as a sedentary lifestyle, obesity and an unhealthy diet are external influences that also contribute to the AGE accumulation pool in the body. The investigators studies support the concept that AGE metabolites represent a biological consequence of the socioeconomic and environmental factors that promote cancer health disparity. This research group examined circulating and tumor AGE levels in clinical specimens of prostate cancer and identified a race specific, tumor-dependent pattern of accumulation.

The aberrant activation and recruitment of immune cells is a major pathogenic consequence of AGE accumulation and a series of studies have highlighted the tumor associated immune response as a critical pathway contributing to cancer disparity. Using patient derived primary tumor cells, the investigators found that AGEs released into the extracellular matrix can recapitulate the tumor associated immune response observed in race specific prostate tumor tissues. Activated immune cells show a similar metabolic profile as a glycolytic tumor cell with a shift towards increased glucose metabolism and aerobic glycolysis (i.e. the Warburg effect). Evidence suggests that abnormal glucose uptake may occur earlier in African American cancer patients with aggressive disease. Further preliminary studies indicate that AGE treatment of prostate cancer cells can alter how cancer cells metabolize glucose to promote an aggressive phenotype.

Based on associations between active metabolism, lifestyle, and race, increases in AGE accumulation may represent a novel biologic mechanism contributing to cancer disparity and may represent a new paradigm to explaining the increased cancer incidence and mortality figures observed within health disparity populations. Given the potential benefits of lifestyle changes and the potential biological role of AGEs in promoting cancer, opportunities exist for collaborations impacting basic, translational, epidemiological and cancer prevention initiatives.

Citation Format: Danzell Smith, Dion Foster, Laura Spruill, Lourdes Nogueira, Bradley Krisanits, Scott Cramer, Marvella Ford, Stephen Savage, Thomas Keane, Victoria Findlay, David Turner. The molecular implications of lifestyle associated metabolites (AGEs) to prostate cancer disparity. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr PR11.