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. © 2010 by Annual Reviews All rights reserved.