Even though obesity alone does not apparently heighten cancer risk in all tissues, there are many prospective epidemiological studies which have demonstrated a direct association between overweight and cancer. About 20% of all cancers are estimated to be caused by excess weight, and approximately half of all cancers in postmenopausal women can be attributed to obesity. The International Agency for Research into Cancer (IARC) and the World Cancer Research Fund (WRCF) reports showed that common cancers in obese people are predominantly endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal. Less common malignancies associated with obesity are malignant melanoma, thyroid cancers, and leukemia, non-Hodgkin’s lymphoma, and multiple myeloma. Furtuermore, data published over the last 25 years emphasize that obesity is a cause of about 20% of deaths from cancer in women while the rate is around 14% in men.
The most popular hypothesis explaining the association between obesity and cancer is that of lower insulin sensitivity. Cancer cells commonly have the ability to respond to the activation effect of insulin, particularly when insulin is highly concentrated, as occurs in obesity. During cancer development, both ERK and PI-3K pathways are triggered by activation of the insulin receptor (IR), as well as IGF-IR, which shows more than 50% of overall sequence homology and even 84% of homology in the tyrosine kinase domain of theα-subunit. Moreover, increased insulin concentrations in portal circulation stimulate GHR signalling and hepatic IGF-I synthesis, while decrease the hepatic expression of binding proteins of IGF-I (IGFBP-1, IGFBP-2), leading to higher plasma levels and bioavailability of free IGF-I, which plays important roles in cancer growth and invasion.
Various other mechanisms such as sex steroids, adipokines, chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function may also take part in the correlation between obesity and cancer.