Obesity related hyperinsulinaemia and hyperglycaemia and cancer development.
Excess body weight in combination with physical inactivity is a major determinant for the development of insulin resistance with associated hyperglycaemia and hyperinsulinaemia and further leads to tumour development. Several prospective epidemiological studies have shown a direct association between excess weight and common malignancies, such as colon, breast (post-menopausal), endometrial, gallbladder, pancreatic, kidney and oesophageal cancers, but also less frequent malignancies, such as leukaemia, multiple myeloma and non-Hodgkin lymphoma. Insulin resistance and hyperinsulinaemia are certainly key biological mechanisms underlying the relationship between adiposity and tumour development. The anti-diabetic drug, metformin, in addition to reduction of insulin resistance has also shown anti-tumour properties, and is increasingly being considered as a drug to prevent and treat obesity-related cancers. Several biological pathways have been involved in the association between excess body weight, insulin resistance and cancer, such as chronic low-grade inflammation, glucose toxicity, AGE product metabolism and the adenosine monophosphate kinase pathway.
Becker
Susen
S
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dossus
Laure
L
Kaaks
Rudolf
R
D015331:Cohort Studies; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D006946:Hyperinsulinism / Q000150:complications* / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism