Impact of the obesity epidemic on cancer.

There is growing appreciation that the current obesity epidemic is associated with increases in cancer incidence at a population level and may lead to poor cancer outcomes; concurrent decreases in cancer mortality at a population level may represent a paradox, i.e., they may also reflect improvements in the diagnosis and treatment of cancer that mask obesity effects. An association of obesity with cancer is biologically plausible because adipose tissue is biologically active, secreting estrogens, adipokines, and cytokines. In obesity, adipose tissue reprogramming may lead to insulin resistance, with or without diabetes, and it may contribute to cancer growth and progression locally or through systemic effects. Obesity-associated changes impact cancer in a complex fashion, potentially acting directly on cells through pathways, such as the phosphoinositide 3-kinase (PI3K) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways, or indirectly via changes in the tumor microenvironment. Approaches to obesity management are discussed, and the potential for pharmacologic interventions that target the obesity-cancer link is addressed.