Obesity, energy balance, and cancer: new opportunities for prevention

Abstract

Obesity is associated with increased risk and poor prognosis for many types of cancer. The mechanisms underlying the obesity-cancer link are becoming increasingly clear and provide multiple opportunities for primary to tertiary prevention. Several obesity-related host factors can influence tumor initiation, progression and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. These host factors include insulin, insulin-like growth factor-I, leptin, adiponectin, steroid hormones, cytokines, and inflammation-related molecules. Each of these host factors is considered in the context of energy balance and as potential targets for cancer prevention. The possibility of prevention at the systems level, including energy restriction, dietary composition, and exercise is considered as is the importance of the newly emerging field of stem cell research as a model for studying energy balance and cancer prevention.

Figure 1

Peptide Growth Factors, Adipokines, Nutrients and Other Putative Factors Involved in Regulating Obesity Related Carcinogenesis. Adapted with permission from Nock and Berger (12) and Cowley and Hardy (161). Factors denoted in bold red text are core features of the Metabolic Syndrome. Factors denoted in bold blue text are additional features that may also be components of the Metabolic Syndrome. Abbreviations used: CRP, C-reactive protein; FFA, free fatty acids; IGF-1, insulin-like growth factor 1; IGFBP, insulin-like growth factor-binding protein; IL-6, interleukin-6; IL-β, interleukin-1β; MAC, macrophage; MCP-1, monocyte chemoattractant protein 1; Mito, mitochondria; PAI-1, plasminogen activator inhibitor-1; ROS, reactive oxygen species; SHBG, steroid hormone-binding globulin; TG, triglycerides; TNF-α, tumor necrosis factor α; VEGF, vascular endothelial growth factor.

Figure 2

Intracellular Pathways Mediating Obesity, Energy Balance and Cancer Intracellular Pathways of Growth Factors Involved in Obesity Associated Cancer Promotion and Progression. Adapted with permission from Nock and Berger (12) and Moore et al (119).