Obesity, type 2 diabetes and risk of digestive cancer.
The frequency of obesity has been increasing worldwide for 20 years. Many epidemiological studies support a correlation between obesity and increased risk of cancer, particularly digestive cancers in both genders, and gynaecological cancer in women. Currently, about 5% of cancers could be directly related to overweight. Carcinogenesis mechanisms induced by obesity involve insulin resistance, adipokine and angiogenic factor secretions, and inflammation. Experimental and clinical evidence suggest that insulin resistance plays a major role in carcinogenesis. Insulin and non-protein banded IGF-1, whose levels are increased in type 2 diabetes, stimulate cellular growth and inhibit apoptosis. Abnormalities in adipokine secretion by the central adipose tissue play a role at different stages of obesity-induced carcinogenesis. Excess of leptin and PAI-1, associated with a decrease in adiponectin secretion in obese people, contributes to carcinogenesis through cellular growth and angiogenesis stimulation. Remodelling of the extracellular matrix due to metalloproteinase stimulation by PAI-1 is also able to promote cell migration. Obesity not only increases cancer frequency, but is also liable to modify the prognosis and the response to antiangiogenic therapy of digestive cancers. This data suggests the need for clinicians to take into account overweight in cancer risk evaluation and to consider obesity and metabolic disorders as confounding factors in designing therapeutic studies.
Hillon
P
P
Université de Bourgogne, CHU de Dijon, rue de l'église, Dijon, France. patrick.hillon@chu-dijon.fr
Guiu
B
B
Vincent
J
J
Petit
J-M
JM
D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D001685:Biological Factors / Q000097:blood; D015992:Body Mass Index; D048909:Diabetes Complications / Q000097:blood / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D019317:Evidence-Based Medicine; D005602:France / Q000453:epidemiology; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D014943:Global Health; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D045726:Metalloproteases / Q000097:blood; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000097:blood
D054392:Adipokines; D001685:Biological Factors; D007328:Insulin; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D007334:Insulin-Like Growth Factor I; D045726:Metalloproteases