Metabolic syndrome, type 2 diabetes, and cancer: Epidemiology and potential mechanisms

Sarit Ben-Shmuel, Ran Rostoker, Eyal J. Scheinman, Derek LeRoith

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

17 Scopus citations

Abstract

Obesity is associated with multiple metabolic disorders that drive cardiovascular disease, T2D and cancer. The doubling in the number of obese adults over the past 3 decades led to the recognition of obesity as a “disease”. With over 42 million children obese or overweight, this epidemic is rapidly growing worldwide. Obesity and T2D are both associated together and independently with an increased risk for cancer and a worse prognosis. Accumulating evidence from epidemiological studies revealed potential factors that may explain the association between obesity-linked metabolic disorders and cancer risk. Studies based on the insulin resistance MKR mice, highlighted the roe of the insulin receptor and its downstream signaling proteins in mediating hyperinsulinemia's mitogenic effects. Hypercholesterolemia was also shown to promote the formation of larger tumors and enhancement in metastasis. Furthermore, the conversion of cholesterol into 27-Hydroxycholesterol was found to link high fat diet-induced hypercholesterolemia with cancer pathophysiology. Alteration in circulating adipokines and cytokines are commonly found in obesity and T2D. Adipokines are involved in tumor growth through multiple mechanisms including mTOR, VEGF and cyclins. In addition, adipose tissues are known to recruit and alter macrophage phenotype; these macrophages can promote cancer progression by secreting inflammatory cytokines such as TNF-a and IL-6. Better characterization on the above factors and their downstream effects is required in order to translate the current knowledge into the clinic, but more importantly is to understand which are the key factors that drive cancer in each patient. Until we reach this point, policies and activities toward healthy diets and physical activities remain the best medicine.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages355-372
Number of pages18
DOIs
StatePublished - 1 Mar 2016
Externally publishedYes

Publication series

NameHandbook of Experimental Pharmacology
Volume233
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

  • Cancer
  • Hyperinsulinemia
  • Obesity

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