Obesity and cancer.

The incidence of obesity in the Western world has increased dramatically during the recent decades. Epidemiological data suggest that obesity is associated with an increased risk of several but not all types of cancers, with clear sex-specific differences. The underlying mechanisms are still a matter of debate. In this review, we discuss the potential factors linking obesity to cancer, with a focus on hormone-dependent cancer types. Current experimental evidence suggests that insulin resistance and a chronic, subclinical inflammation in the visceral fat are the major metabolic events, causing alterations in the levels of insulin, glucose, free fatty acids, insulin-like growth factor-1 and -2, adipose tissue-derived proinflammatory factors (tumor necrosis factor-α and interleukin-1, -6, -12, and -23), and other bioactive molecules such as adipokines (adiponectin and leptin), vascular endothelial growth factor, sex hormones, gut microbiota, and secondary bile acids. All these factors may act directly or indirectly on the tumor microenvironment to drive tumor progression via the stimulation of cell survival/antiapoptosis, cell proliferation, angiogenesis, and invasion/metastasis of cancer cells. Therapeutic strategies (including bariatric surgery) that target dysfunctional or inflamed fat have been shown to benefit patients, whereas other cell- or hormone-directed interventions (such as the conversion of visceral fat macrophages to an anti-inflammatory M2 phenotype or the pharmacological modulation of serum adipokine levels) are still theoretical and need to be clinically evaluated for their ability to successfully treat or prevent obesity-related cancers.