Linking Race, Cancer Outcomes, and Tissue Repair

Abstract

The burden of cancer in the United States is unevenly spread across its different populations, with stark differences in both disease prevalence and outcome on the basis of race and ethnicity. Although a large portion of these differences can be explained by a variety of sociobehavioral and socioeconomic factors, even after these exposures are taken into consideration, considerable disparities persist. In this review, we explore a conceptual framework of biological theories and unifying concepts, based on an evolutionary perspective, that may help better define common guiding principles for exploration of underlying causes of cancer health disparities. The ultimate goal of this conceptual perspective is to outline approaches that may aid in establishing integrated pathway and processes analyses to provide useful insights to guide the development of future interventions. These interventions will improve outcome, increase prevention, and ultimately eliminate all disparities.

Figure 1

Schematic illustration of cellular plasticity in the macrophage and fibroblast in the healing wound and the secreted growth factors, cytokines, and other factors that drive the phenotypic transitions. ACTA2, smooth muscle α-2 actin; Arg, arginine; CCL, C-C motif chemokine ligand; CD206, cluster of differentiation; Col1A, collagen type I α; CXCL, C-X-C motif chemokine; EGF, epidermal growth factor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; IFN, interferon; LOX, lysyl oxidase; MMP, matrix metalloproteinase; P3, forkhead box P3; PDGF, platelet-derived growth factor; SDF, stromal cell-derived factor; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinase; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; YM1, β-N-acetylhexosaminidase Ym1.

Figure 2

A: Flowchart of association of influences and properties of tissue repair and cellular plasticity that are causative drivers of cancer and other diseases in which mesenchymal transitions play a major role. B: Ideogram of chromosome 8q24 associated genes that have roles in epithelial-to-mesenchymal transition and stem cell-like properties. ESRD, end-stage renal disease.