The most important questions in cancer research and clinical oncology—Question 2–5. Obesity-related cancers: more questions than answers

Abstract

Obesity is recognized as the second highest risk factor for cancer. The pathogenic mechanisms underlying tobacco-related cancers are well characterized and effective programs have led to a decline in smoking and related cancers, but there is a global epidemic of obesity without a clear understanding of how obesity causes cancer. Obesity is heterogeneous, and approximately 25% of obese individuals remain healthy (metabolically healthy obese, MHO), so which fat deposition (subcutaneous versus visceral, adipose versus ectopic) is “malignant”? What is the mechanism of carcinogenesis? Is it by metabolic dysregulation or chronic inflammation? Through which chemokines/genes/signaling pathways does adipose tissue influence carcinogenesis? Can selective inhibition of these pathways uncouple obesity from cancers? Do all obesity related cancers (ORCs) share a molecular signature? Are there common (over-lapping) genetic loci that make individuals susceptible to obesity, metabolic syndrome, and cancers? Can we identify precursor lesions of ORCs and will early intervention of high risk individuals alter the natural history? It appears unlikely that the obesity epidemic will be controlled anytime soon; answers to these questions will help to reduce the adverse effect of obesity on human condition.

Obesity-related Cancers: The Coming Epidemic

“…[73] Research on the molecular mechanisms of ORCs is crucial. [74] It is well known that Indians develop cardiometabolic complications of obesity at much lower levels of BMI (for which modified criteria have been suggested [75] ); whether similar risk exists for ORCs is a potential area for study.…”

The Troubling Link Between Non-alcoholic Fatty Liver Disease (NAFLD) and Extrahepatic Cancers (EHC)

“…The molecular links between obesity and cancer have been speculated on [ 66 ]; recent reviews have addressed the molecular mechanisms tying NAFLD to HCC [ 67 ] but the remote effects of NAFLD leading to EHC are less clear. The hormones, insulin and insulin-like growth factor-1 (IGF-1) have been implicated with some evidence [ 68 ].…”

Progranulin: A proangiogenic factor in visceral adipose tissue in tumoral and non‑tumoral visceral pathology

“…This crosstalk is made possible by the active secretion of adipokines or adipocytokines from the adipose tissue with metabolic and pro/anti-inflammatory effects ( 9 ). As a consequence, there is a direct link between obesity, cardiovascular diseases and in the last 10 years cancer development ( 1 , 10 , 11 ).…”