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.
Roberts
Darren L
DL
Clinical and Experimental Pharmacology, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Manchester, UK.
Dive
Caroline
C
Renehan
Andrew G
AG
D054392:Adipokines / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D012737:Sex Factors; D013002:Somatomedins / Q000502:physiology
D054392:Adipokines; D012739:Gonadal Steroid Hormones; D007328:Insulin; D013002:Somatomedins