Insulin, insulin-like growth factors and colon cancer: a review of the evidence.
Insulin and insulin-like growth factor (IGF) axes are major determinants of proliferation and apoptosis and thus may influence carcinogenesis. In various animal models, modulation of insulin and IGF-1 levels through various means, including direct infusion, energy excess or restriction, genetically induced obesity, dietary quality including fatty acid and sucrose content, inhibition of normal insulin secretion and pharmacologic inhibition of IGF-1, influences colonic carcinogenesis. Human evidence also associates high levels of insulin and IGF-1 with increased risk of colon cancer. Clinical conditions associated with high levels of insulin (noninsulin-dependent diabetes mellitus and hypertriglyceridemia) and IGF-1 (acromegaly) are related to increased risk of colon cancer, and increased circulating concentrations of insulin and IGF-1 are related to a higher risk of colonic neoplasia. Determinants and markers of hyperinsulinemia (physical inactivity, high body mass index, central adiposity) and high IGF-1 levels (tall stature) are also related to higher risk. Many studies indicate that dietary patterns that stimulate insulin resistance or secretion, including high consumption of sucrose, various sources of starch, a high glycemic index and high saturated fatty acid intake, are associated with a higher risk of colon cancer. Although additional environmental and genetic factors affect colon cancer, the incidence of this malignancy was invariably low before the technological advances that rendered sedentary lifestyles and obesity common, and increased availability of highly processed carbohydrates and saturated fatty acids. Efforts to counter these patterns are likely to have the most potential to reduce colon cancer incidence, as well as cardiovascular disease and diabetes mellitus.
Giovannucci
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Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. giovannucci@channing.harvard.edu
D000172:Acromegaly / Q000097:blood / Q000150:complications; D000818:Animals; D017209:Apoptosis; D015992:Body Mass Index; D002455:Cell Division; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000209:etiology*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D015444:Exercise; D006801:Humans; D007328:Insulin / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008019:Life Style; D009765:Obesity / Q000150:complications; D012307:Risk Factors
D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I