Endocrine Abstracts

The global obesity epidemic needs no introduction to endocrinologists, but there has also been a parallel growing epidemic in the common epithelial cancers (breast, colorectum and prostate) that has largely coincided in timing and geography. Obesity has some clear effects that may increase the propensity for the development of specific tumors. There are however broader effects that could impact more generally on the most common epithelial cancers. Epithelial cells form barriers in the body that have to be constantly replenished, requiring rapid cell turnover throughout life with a consequence that naturally occurring mutations accumulate with aging. The explosion of genome sequencing data has confirmed this accumulation and revealed the build up of huge numbers of mutations in normal epithelial tissues with advancing years. These numerous mutations are more than sufficient to initiate carcinogenesis, and as a consequence elderly individuals develop many occult neoplastic lesions in epithelial tissues, as consistently confirmed by autopsy studies. Most of these lesions will however not progress to become life-threatening cancers. Such progression appears to depend on context: the tissue ecosystem within our body. This implies that the initiating mutations are not rate limiting and the transformed ‘seeds’ can be plentiful but they only ‘germinate’ into clinical cancers if the ‘soil’ is right. The incidence of these cancers is much lower in the East, but is increasing with Westernisation, and increases more acutely in migrants to the West. Epidemiology has also indicated that metabolic biomarkers are prospectively associated with the incidence and poor prognosis of exactly the same cancers. A Western lifestyle is strongly associated with perturbed metabolism and obesity: these may then provide a fertile soil within the body that could enable the progression of epithelial cancers. Obesity and the associated metabolic disturbance are characterised by insulin resistance and increased levels of glucose and other metabolites, dyslipidemia and altered levels of adipokines, cytokines and growth factors.The latent neoplastic seeds, which naturally accumulate with age, may then be more likely to germinate and grow in this more fertile soil. Evidence from many different fields is increasingly indicating that for the common epithelial cancers our lifestyles and especially our metabolic health, rather than our genes, may be more important for their progression to life-threatening disease. This raises new opportunities for different strategies for prevention and treatment of these cancers.