How Excessive Energy Promotes Cancer

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Excessive energy intake leads to obesity, type 2 diabetes, and chronic inflammation. All three of these are also major risk factors for numerous types of cancer. However, the mechanism by which cancer evolves in people with these conditions is not well understood. Most of the research linking excessive energy intake to cancer comes from observational studies that cannot establish causality. The figure below shows the cancers most closely linked to obesity:

A recent study published in Evolution, Medicine and Public Health offers an intriguing possibility as to how excess energy intake may super-charge cell growth and contribute to some mutated cells turning into deadly cancers.
It is believed that cancer develops due to mutations that arise in an individual cell and these mutated cells divide rapidly within a tissue, which in turn leads to a tumor. However, recent studies have suggested that these initial genetic mutations are very common in many cells but do not usually lead to the development of cancer. Dr. John Pepper, a biologist with the National Cancer Institute’s Division of Cancer Prevention and an External Professor at the Santa Fe Institute realized that mutations alone cannot be the sole reason a mutated cell gives rise to a cancerous growth.

Healthy cells and tissue have built-in limiters that keep cells from proliferating out of control. It appeared that excessive calorie intake, which drives diabetes, obesity, and inflammation may be overwhelming those built-in limiting factors. An overabundance of energy may overwhelm the tissue’s ability to limit proliferation. Dr. Pepper and his colleagues, Daniel Wu of Stanford University and C. Athena Aktipis of Arizona State University, building on previous work done in France, believe that an oversupply of energy may be an important factor leading to over-proliferation when mechanisms that strictly limit the energy supply to cells are overcome by an oversupply of energy. The team ran a computational model to see what effect excessive energy supply might have and found that such an overload of energy did indeed cause a large increase in cell production that could lead to cancer growth. Dr. Pepper’s simulation experiment suggested that under plausible biological assumptions, elevated energy supply to a tissue could lead to the evolution of elevated energy uptake by cells, leading to the evolution of the two defining traits of cancerous cells which include both rapid growth and the ability of these rapidly-dividing cells to invade surrounding tissues. Dr Pepper et. al conclude: “Our results support the hypothesis of metabolic cancer suppression, suggesting that vascular oversupply of energetic resources to somatic cells removes normal energetic limitations on cell proliferation, and that this accelerates cellular evolution toward cancer. Various predictions of this hypothesis are amenable to empirical testing and have promising implications for translational research toward clinical cancer prevention” (1).

Of course, empirical studies are still needed to confirm these findings. Nevertheless, this study lays the groundwork for what could be an important advance in cancer prevention research — an area that deserves increased attention, according to Dr Pepper. Other research suggests that epigenetic changes triggered by excessive energy intake and obesity. Epigenetic changes to the cell’s DNA and associated chromatin proteins are increasingly being considered as important mediators of the linkage between increasing obesity prevalence is contributing to higher rates of many common cancers (2).

Bottom Line: Growing research is helping to explain why following a healthy diet, exercising regularly, and reducing excess body fat and keeping it off will also help reduce the risk of developing numerous types of cancer. It also suggests that adopting a healthy diet and exercise program may slow or stop some cancer cells from proliferating as well. The results provide a plausible physiological mechanism to explain why adopting a healthy diet and exercise program and losing and keeping off excessive body fat stores may even help those with some types of cancer by removing the stimulation for these cancerous cells to grow more rapidly and spread more quickly.

By James J. Kenney, PhD, FACN

References:

1.  https://doi.org/10.1093/emph/eoz004
2. http://cancerpreventionresearch.aacrjournals.org/content/11/3/125