Breast cancer, despite the huge improvement in diagnostic techniques and the development of targeted and more effective therapies, yet remains one of the leading causes of death in Western countries. In addition, it is now clear that we are facing a "pandemic" global obesity, which currently affects hundreds of millions of women and men not only in the developed world, but also in many countries in the developing world
Obesity is commonly associated with metabolic syndrome, which includes a variety of conditions ranging from insulin resistance, type 2 diabetes, hyperlipidemia, hypertension, increased risk of cardiovascular disease, stroke and kidney failure. It is currently recognized that the metabolic syndrome associated with obesity is a risk factor for a number of tumors. In particular, it was shown that both obesity and type 2 diabetes increase the risk of developing breast cancer in post-menopausal women. The molecular mechanisms that link obesity and increased risk of developing breast cancer, are not yet known. The data in the literature suggest that the increase in the risk of breast cancer in post-menopausal women is due to an excessive estrogen production by adipose tissue. The synthesis of estrogen in adipose tissue increases with obesity, but also with aging and is associated with an increase in expression of the enzyme aromatase, which is responsible for the biosynthesis of estrogen. In addition, obesity is often associated with metabolic disorders such as insulin resistance, type 2 diabetes and hyperinsulinemia and it is thought that high levels of insulin as well as IGF are a further cause of breast cancer increased risk. So it is assumed that the correlation between obesity and breast cancer is due to excessive production of estrogen and insulin and IGF. However, the molecular mechanisms by which estrogen, insulin and IGF determine the onset of breast cancer are not known.
The identification of the molecular mechanisms by which estrogen, insulin and IGF determine the onset of breast cancer is crucial not only for diagnostic purposes but especially for the development of new, effective therapies for the treatment of post-menopausal women suffering from obesity.
Therefore, we propose to identify these key molecular mechanisms underlying the link between obesity, metabolic syndrome and breast cancer in post-menopausal women. With the help of pathologists we will first select a group of patients that are post-menopausal, obese and affected by breast cancer. Breast cancer samples and normal counterpart will be subjected to high-throughput RNA sequencing, to identify the most interesting differences in gene expression levels. This analysis will allow us to identify the putative candidate genes that are involved in the relationship between obesity and breast cancer. the identification of the genes involved will permit to identify diagnostic and therapeutic markers to patent and eventually to develop by pharma industries