Obesity and cancer: from molecular mechanisms
to disease prevention
Molecular Oncology Group
One of our main lines of investigation is the association between obesity and cancer prognosis with special focus in the direct implication of excessive adipose tissue in tumor microenvironment. The dietary patterns have changed during the last decades: the physical activity has decreased in parallel with a significant increase in caloric intake. This energetic imbalance gives rise to a metabolic shift that generates hypertrophy and hyperplasia of adipose tissue leading to overweight and eventually to obesity. According to The World Health Organization (WHO), nowadays 13% of the overall adult population worldwide are obese.
An unquestionable cause of concern is that in 2014, 41 million children under the age of 5 years were overweight or obese (WHO). Obesity has been implicated in the development of cardiovascular diseases and type-2 diabetes1 as well as in the initiation and dissemination of several types of cancer2 . In fact, overall risk of death from cancer is 1.5-1.6-fold higher in men and women with a BMI>40Kg/m3 . There are not enough data supporting the reversibility of obesity effects when the patients are already diagnosed for cancer. Thus, we should fight against obesity earlier in age and raise awareness about the importance of keeping healthy habits in the youngest population. Social education for health promotion, the individual responsibility as well as the food industry together with basic and translational research need to team up to face this urgent global health challenge.
The main types of cancer whose increased risk has been associated with obesity are: prostate cancer4 , postmenstrual endometrial5 and breast cancer2 , ovary6 , bladder7 , liver8 , colon9 , pancreas2 , esophageal10, gallbladder11, kidney12 and thyroid cancer13 (Table 1). The excess of visceral adiposity provokes alterations in cellular composition of adipose tissue which is crucial for growth and dissemination of tumors that grow in a microenvironment rich in adipocytes like breast, ovary or colon tumors14. Although the epidemiological data are strong, the molecular mechanisms associating obesity and cancer are still poorly understood.
So far, three hypotheses have been defined to link obesity and tumor progression: alteration in the rates of androgenic precursors to oestradiol conversion leading to a hormonal imbalance; insulin resistance and the excess of bioactive IGF1 and systemic inflammation due to and excessive adipokine signaling activation15, 16 (Figure 1). Our main goal is to shed light in new mechanisms linking both pathologies. We focus our research in understanding how lipid metabolism and specially cholesterol imbalance due to excessive adipose tissue in the tumour vicinity could influence cancer progression and dissemination.
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