Biological Mechanisms Linking Obesity and Cancer Risk: New Perspectives

Body mass index, as an approximation of body adiposity, is associated with increased risk of several common and less common malignancies in a sex- and site-specific manner. These findings implicate sex- and cancer site–specific biological mechanisms underpinning these associations, and it is unlikely that there is a “one system fits all” mechanism. Three main candidate systems have been proposed—insulin and the insulin-like growth factor–I axis, sex steroids, and adipokines—but there are shortfalls to these hypotheses. In this review, three novel candidate mechanisms are proposed: obesity-induced hypoxia, shared genetic susceptibility, and migrating adipose stromal cells. While public health policies aimed at curbing the underlying causes of the obesity epidemic are being implemented, there is a parallel need to better understand the biological processes linking obesity and cancer as a prerequisite to the development of new approaches to prevention and treatment.