Why does obesity promote cancer? Epidemiology, biology, and open questions

The association between obesity and/or metabolic syndrome and an elevated mortality from cancer has been confirmed by an astonishing number of studies across nations and ethnicities, such that obesity is now recognised to be among the most prominent cancer risk factors worldwide. Despite this overwhelming evidence and the societal impact of obesity, we know surprisingly little about the underlying molecular mechanisms. This knowledge gap is a major obstacle to the implementation of effective lifestyle change policies. As the scientific community is insecure on what messages it should deliver, administrators are uncertain as to what exactly to recommend, and consumers are confused about whom to believe. This leaves the field flooded with pseudo-scientific recommendations that are hard to eradicate. In this review, I will provide a summary of the existing epidemiological and mechanistic evidence on the relationship between systemic metabolism and cancer, highlighting debated issues and ongoing investigations.