A Conversation With

John Milner, Ph.D.

Chief, Nutritional Science Research Group
Division of Cancer Prevention

Please tell us about the Nutritional Science Research Group.

The Nutritional Science Research Group (NSRG) in the Division of Cancer Prevention (DCP) plans, develops, and coordinates external research programs in diet and nutrition as they relate to cancer prevention. The NSRG works with external researchers and internal NCI staff to foster the development of quantitative methods to monitor nutritional exposures, and to identify the molecular action of foods and their components.

For example, some of the NSRG projects focus on determining how essential nutrients (such as calcium in dairy products or non-essential components such as sulforaphane in broccoli) influence specific genes and ultimately the associated molecular targets. The overarching goal is to identify people who will benefit most and those who might be placed at risk due to dietary change. The NSRG has a diversified grant portfolio which includes research focused on ways in which the approximately 25,000 food components influence the cellular processeses that are key to influencing cancer risk and tumor behavior.

The NSRG publishes the quarterly Nutrition Frontiers newsletter (http://prevention.cancer.gov/programs-resources/groups/ns/nutrition-frontiers), runs the Frontiers in Nutrition and Cancer Prevention Online CME series (http://prevention.cancer.gov/programs-resources/groups/ns/webinars), and writes numerous fact sheets about cancer prevention (http://prevention. cancer.gov/programs-resources/groups/ns/factsheet). Many training and fellowship opportunities exist in cancer and nutrition research within the NRSG, including sabbatical opportunities for interested researchers (http://prevention.cancer.gov/programs-resources/groups/ns/ training).

Q. Can you share a few promising research projects funded by your office in the areas of nutrition, diet, and cancer prevention?

It is very difficult to say that one study is more important than another, but the ongoing VITamin D and OmegA-3 TriaL (VITAL) study is unique because of its large size and the focus on both of these food components (vitamin D and omega-3 fatty acids) as potential promoters of health. VITAL is a research study of 20,000 men and women across the United States that investigates whether taking daily dietary supplements of vitamin D3 or omega-3 fatty acids reduces the risk of developing cancer, heart disease, and stroke, in people without a prior history of these diseases*. This is a large-scale U01 trial that is cofunded with The National Heart, Lung, and Blood Institute (NHLBI) and NIH Office of the Director (OD).

VITAL is a 5-year study headed up by JoAnn Manson, M.D., and Julie Burning, Sc.D. at Brigham and Woman’s Hospital, in Boston, Massachusetts. Gabriela Riscuta, M.D., CNS, is the Program Director of the VITAL trial within the NSRG. The study is recruiting incredibly well and although it is only in its initial phase, everything we have been hearing from the study group sounds promising. More information about VITAL is available on the VITAL website (http://www.vitalstudy.org/) and in the NIH Reporter Database (http://projectreporter.nih.gov/project_info_details.cfm?aid=8120386&icde=12225940)

We fund many other studies throughout the United States that have shown interesting results. We profile several of them in our Nutrition Frontiers quarterly newsletter that includes studies and results that we find relevant and useful to researchers and the public.

We recently profiled a study by Li-Shu Wang and colleagues from the Ohio State University Comprehensive Cancer Center, which showed that black raspberries might modulate colorectal tumor development. This pilot study had patients consume 60 grams of black raspberry powder daily for an average of 4 weeks. After the treatment period, biopsies were performed on tumor tissue and adjacent normal tissue and revealed that black raspberries decreased cancer cell growth and tumor blood vessel formation and increased cancer cell death. While a pilot study, the findings are intriguing.

Q. Do you find that conducting research on bioactive food components poses any significant challenges?

A challenging question related to nutrition research is: “When does a food component become a drug?” This is a situation that has profound regulatory issues for the Food and Drug Administration. For example, if resveratrol (found in red wine) has an active anticancer effect on the body, how much wine does someone have to consume to achieve those beneficial effects? In addition, if you cannot consume wine or in the quantity needed, yet you can take it in pill form with exaggerated amounts, is it now considered a drug? We must be aware of the amounts and duration of exposures that are required to bring about a response and thus if this is a physiological or pharmacological response.

We are also perplexed by inconsistencies in the research literature about the importance of specific dietary components, just as people may be seeing in the media or hearing from their doctors. For example, some research studies suggest fish oil (omega-3 fatty acids) may help to inhibit cancer while others provide no evidence for a benefit. Many other foods and beverages (such as fruit or coffee) suffer from the same inconsistencies in findings. Part of the reason for this is because historically we’ve done a rather poor job of assessing nutritional intake. In addition, we have not considered individuality in response, that is, that different people respond to food and bioactive food components in different ways that likely depend on their genes. Both of these issues can lead to mixed messages about how important diet is in our lives — especially as a deterrent to cancer.

Overall, we believe that over 30% of cancers are preventable by dietary change; however, that does not mean that every person needs to adhere to the same type of diet plan. Certain people will likely get more benefit from a specific dietary change, say a vegan diet, than someone else. That second person may respond better to different dietary change including increased fish intake. The science is headed in the direction of personalized nutrition and the idea that some subpopulations may be more responsive to certain diets than others. Identification of these folks will be done through the practice of nutrigenomics, or the study of the interactions of food and their active components with a person’s particular genes. If one knows something about a person’s genes and how they are functioning, then predictions about whether or not one will benefit from specific foods can be made.

Q. What would you say are some common misconceptions people have about nutrition and its role in cancer prevention, and what does the research say about these misconceptions?

The number one misconception is the idea that “one size fits all” for nutrition. The other common misconception with nutrition and cancer prevention is “if a little is good, a lot is even better.” Nutrition is a complex area of study. There are over 25,000 bioactive food components, at least, and the diet we eat is not simple. While there is an overall 20% increase of cancer incidence in those that are obese, certain types of cancer are much more affected by obesity than others.

Information about how food and bioactive food components affect you and your cancer risk are available from lots of different sources. We in the NSRG have a set of fact sheets that give basic information about vitamin D and cancer prevention, calcium and cancer prevention, garlic and cancer prevention, and several others. View all the factsheets here: http://prevention.cancer.gov/programs-resources/groups/ns/factsheet.

Q. Where do you think nutrition research will go next?

There is certainly growing recognition about how excess calories can negatively affect disease risk, including cancer. It might not always be the excess calories, it may be that when you are consuming excess calories you are not consuming something else, thus creating an inadequacy of one or more nutrients.

Also, from my perspective we are incorporating a personalized approach to health promotion, and moving away from this “one size fits all” belief. Multiple factors, including the microbiome (the environment of microbes and viruses that are in our gastrointestinal tracts), can be influenced by the types of foods that we consume and, in turn, influence the response to our foods. This area deserves additional attention.

Lastly, I think more and more people are becoming aware of a “transgenerational effect” between diet and disease. The transgenerational effect posits that what one does influences his/her offspring and their offspring. For example, there is some evidence that a parent’s diet may influence their child’s subsequent risk of disease state, including cancer,and that depending on the food item this can happen from both the father’s or mother’s side. Overeating in animals seems to lead to overeating in the offspring for multiple generations. So we must begin to ask what the impact of the current obesity crisis will be, not only on us but on future generations as well. Hopefully, we will continue to make more discoveries and gain greater understanding of transgenerational effects of eating behaviors.

Q. Where do you see the research from this office headed? Do you have goals when it comes to the types of research you would like to see coming through the Nutritional Science Research Group?

The NSRG continues to promote basic nutrition science since there is so much to learn about the actions of food components in healthy and unhealthy circumstances. Without understanding the variability in response, many may simply dismiss diet as one variable for health and disease prevention. We need knowledge about mechanisms and who benefits most if we are to translate science into appropriate advice for people about what to eat.

We are keen to learn more about the microbiome and its influence on the response to foods and their components. We want to know what the optimum time is for ingesting a specific food or bioactive food component to get the greatest response. This has to do with circadian rhythms — our 24-hour biological clock. Should one eat a specific food/component at one time of day or another, and/or with something else to obtain maximum benefits? In addition, we need to know how to optimize a cell and keep it resilient from any kind of damage, whether caused by excess calories, environmental toxins, bacteria, or viruses.

We are also exploring what specific cell types are most influenced by diet. For instance, we are intrigued with the potential impact of dietary components on stem cells, both normal stem cells and cancer stem cells. The stem cells in the tumor are abnormal because they are growing at an uncontrolled rate, but it can be argued that something similar is happening in normal cells that are involved with repairing tissue damage. We also need to understand why food components often seem to influence cancer risk in one type of tissue more than another. If the response were in stem cells, why would not all tissues respond identically?

The other big area that always surfaces is how do isolated food components compare with the whole food. We are often asked,“Is a supplement the same as a food?” We just do not have as much data as needed to answer that question. Foods have multiple components that may act together to enhance or maybe suppress the effects of one constituent. Interactions between various nutrients are most assuredly an area of great interest to the NSRG.