Genomic variations can drive differences in the way people benefit from nutrients — an idea that may lead to individualized anticancer diets.
The emerging field of molecular medicine promises a new era of cancer care — earlier and more precise diagnosis, and individualized therapy that is more effective with fewer side effects. Developing as part of that field is a greater understanding of the genetic terrain that links diet to the development of cancer and other diseases.
The connection between diet and health is well-known in a general sense. Consuming too much sugar and fat can lead to obesity and diabetes. An insufficient amount of any vital dietary constituent can result in illness — for instance, in cases where a lack of vitamin C leads to scurvy.
Molecular medicine takes the view down to the level of DNA, the 20,000 or so genes that encode the biological software that operates the human machine, collectively known as the genome. Nutrigenomics is the study of the effects of foods on the expression of genes, and how individual genetic differences guide the body's response to nutrients.
"We're interested in studying the biology of nutrition, the influence of genetic makeup on the effects of nutrients," says Sharon Ross, Ph.D., M.P.H., program director for the Nutritional Science Research Group of the National Cancer Institute.
One gene that has been studied intensively is APOE, which contains instructions for the manufacture of lipoprotein, a molecule involved in cholesterol transport and metabolism. Variations in the APOE gene can cause high cholesterol levels that may, in turn, contribute to cardiovascular disease or even prostate or other cancers, and those with certain variations may benefit from either a low-fat, high-carbohydrate diet or a high-fat, low-carbohydrate diet. Testing for these gene variations may be useful as a way of assessing an individual's risk of developing various related disorders and then choosing appropriate approaches to prevention or treatment.
Vitamin D is a nutrient that has been found to be quite active at the genomic level. According to a report published in the August 2010 issue of Genomic Research, the vitamin D receptor exists at 2,776 sites in the genome, including many areas close to active genes; the paper’s authors identified 229 genes whose expression changes in response to vitamin D. A 2006 review of the medical literature that appeared in the American Journal of Public Health found that “sufficient vitamin D status” helped to lower the risk of death from colon, breast, ovarian and prostate cancers, and suggested vitamin D supplementation when needed — although experts caution that too much vitamin D can also cause health problems, so doctors should be consulted.
Deficiencies in dietary folate — an essential B vitamin — are linked to DNA damage and an increased risk of colon cancer. However, Lorenzo Cohen, Ph.D., director of the Integrative Medicine Program at MD Anderson Cancer Center, notes that an individual's response to folate deficiency depends on his or her genes, as does a person's risk of colorectal cancer associated with eating red meat.Steven H. Zeisel, M.D., and colleagues at University of North Carolina Chapel Hill are studying the role of choline — a nutrient required for the neurotransmitter acetylcholine — in cell proliferation and programmed cell death (apoptosis). Both mechanisms are involved in the development of cancer.
Studies show that mice fed a diet deficient in choline develop liver cancer, and humans who don’t get enough choline may develop a fatty liver and an increase in cell suicide in the liver. In humans, the need for dietary choline varies by age and gender. Most young women don't need it — so long as they have a functioning liver enzyme known as PEMT. The gene that expresses PEMT is influenced by estrogen, so men and postmenopausal women need choline in their diets to remain healthy.
Zeisel's group discovered that 45 percent of women have a variation in the PEMT gene that is not affected by estrogen. These women have about a 30 percent increased risk of breast cancer, and may benefit from dietary choline, according to Zeisel.
Even the genomics and diversity of the bacteria in our guts and skin (known as our “microbiome”) can be affected by diet and drugs, and might influence our bodies’ ability to resist disease, including cancer — an area that is getting much attention and research funding.
Imagine getting a genetic test to tell you how much folate or choline is ideal for you — or, even better, an individualized dietary prescription based on your genome, proteome (all proteins in the body) and metabolome (all metabolic activity). Science isn't there yet, but is headed in that direction.
"Are we there yet for population-based recommendations? I don't think so," Ross says. "We're still figuring it out on a population level, much less on an individual level."
Steven P. Novella, M.D., a Yale neurologist and founder of the Science-Based Medicine blog, says that much of the nutrigenomic research to date has been in cells or animals, and is not yet ready for prime time. "Extrapolating from these preliminary results can lead to the wrong conclusion," he says. "It takes years for the science to play out before we can make inferences."
Until nutrigenomics comes to fruition, Novella says, the typical time-honored advice still holds true: Exercise regularly and eat a balanced diet that includes plenty of fresh fruits and healthful vegetables.