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You Are What You Eat: Linking Nutrition, Metabolism and Cancer

As the obesity epidemic climbs, and the connection between nutrition and its effects on health risks and outcomes are top of mind, Wistar’s most recent Women & Science Program featured a comprehensive talk on how what we eat is used by our cells for energy, and the connection to cancer development. The first program of this year was held fittingly during the week of International Day of Women and Girls in Science.

Guest speaker Kathryn Wellen, Ph.D., associate professor in the Department of Cancer Biology and the Abramson Family Cancer Research Institute at the University of Pennsylvania, took the audience on a journey through biochemistry, genetics and cell biology to explain how nutrition steers the cells’ metabolic choices and cancer behavior. 

Wellen’s research centers on the mechanisms through which cells monitor the availability of nutrients, which are as critical as the fuel gauge in our cars. The answer lies in the epigenetic control of gene expression, or the mechanisms that cause genes to be switched on and off. Every cell in our body contains the same DNA sequence, but the way this is read changes from cell type to cell type and in response to environmental stimuli. This regulation happens through chemical modifications of DNA and its associated proteins.

A stunning example that Wellen gave of the environmental effect on gene expression and, as a consequence, on human health is the case of the famine that plagued part of the Dutch population towards the end of World War II. Babies conceived during that time were born heavier than normal and grew up to experience higher rates of obesity, diabetes and schizophrenia. The starvation in the Dutch Hunger Winter, as it is known, altered expression of certain genes in unborn children, and these alterations remained in place for the rest of the children’s lives, affecting their health.

As Wellen explained, at the cellular level what we eat is broken down into metabolites that are needed to carry out the chemical modifications of DNA required for epigenetic regulation of gene expression. Wellen studies these mechanisms and the influence of different nutrients on the activity of genes that are critical in cancer.

In the early 1900s, the first observation on the relation between metabolism and cancer came from Nobel laureate Otto Warburg, who discovered that cancer cells utilize different metabolic pathways than normal cells. With the discovery of the role of gene mutations in causing cancer, scientists realized that mutations can alter genes that control metabolism. The latest piece to the puzzle is being added by the work of Wellen and others that connects metabolic changes to epigenetic changes.

Many recent studies point to obesity as a strong risk factor for several types of cancers. Wellen cautioned about the critical role of nutrition in cancer prevention. Research has linked sugar consumption to obesity, an epidemic on the rise in the country. In the 1700s, the average amount of sugar consumed per person was four pounds a year; however, by the 1990s this number had spiked to a shocking 120 pounds a year.

Research also shows that diet can impact therapeutic responses in cancer patients, for example by regulating insulin levels. In broader terms, because of the link between metabolism and gene regulation, it is likely that adjusting patients’ diets could make a difference in how therapy works for them.

Wellen believes that a deeper understanding of these intricate conversations between diet, metabolism, epigenetics, and cancer is needed because it may point to vulnerabilities that could be exploited from a therapeutic perspective.

 

Women & Science - February 13, 2019