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What we eat and its potential effect on cancer prevention has interested scientists since the 1950s. Now, more than half a century later, researchers are still trying to determine how various foods and micronutrients impact the disease.
In the early stages of diet and nutrition research, many descriptive studies noted the widely disparate cancer rates for different populations around the world, and the changes that occur when one population migrates to another location with different lifestyle and diet factors, says Robert Hoover, MD, ScD, director of the National Cancer Institute's Epidemiology and Biostatistics Program. “Up until fairly recently, we didn't have much to show for specific foods and nutrients, but we did see certain patterns,” says Dr. Hoover. Those patterns included observations that people who ate more fruit and vegetables and less red meat generally had lower rates of certain cancers. Nevertheless, it was difficult to pinpoint what roles specific foods played in the disease.
JoAnn E. Manson, MD, PhD, chief of preventive medicine at Brigham and Women's Hospital in Boston, Massachusetts, adds that in the past, many vitamins, supplements, and micronutrients have appeared promising in reducing cancer rates in observational studies and then, “when put to the test in randomized clinical trials, the benefits were not found, and even some risks were identified.”
The recent revolution in molecular science, however, provides a new focus for food and nutrition research related to cancer. Specifically, the field of metabolomics (the study of chemical processes involving metabolites) will enable researchers to use metabolic profiling to give an instantaneous snapshot of the physiology of a cell. The field has led to a better understanding of both diabetes and heart disease, and also will enable better analysis of cancer, says Dr. Hoover. “The cancer community looks at some of these diseases as metabolic diseases, and we have felt for a long time that they could be related to what you eat,” he says.
One challenge to conducting dietary studies is the difficulty in measuring what people have eaten over the course of their lives. It is difficult for most people to remember what they ate today let alone what they ate 30 years ago when it may have been important, says Dr. Hoover.
Scientists, however, can examine metabolites in the blood and uncover systems that have gone awry based on what people have eaten over their lifetimes, as well as other factors such as their weight and how much they exercise. Using these tools in conjunction with those from microbiomics-which measures how much bacteria a person has in their bowel, mouth, and skin and also plays a role in metabolism-researchers will be able to better determine specific biomarkers related to these diseases, Dr. Hoover says.
Scientists also will be able to develop genetic profiles of obese individuals and determine whether one profile is worse than another. Furthermore, they will be able to use specific biomarkers to test whether cancers such as those of the breast and endometrium are due to estrogen, inflammation, or another factor. “We've learned some important things in public health that have ramped up in the last 10 years with molecular technology, and now we have the tools to let the human body tell us what's important,” adds Dr. Hoover.
He also notes that other methods of improving dietary research include finding better ways of measuring what people eat. One example is having study participants use their cell phones to take pictures of what they eat to better measure portion size. He also believes researchers need to improve ways of assessing the actual characteristics of diet in migratory populations. “No one has investigated these different diets very well,” he says.
Vitamin D Correlation
Researchers continue to pursue answers to important questions about micronutrients, which are somewhat easier to hone in on than different foods. Dr. Manson, for example, is leading the Vitamin D and Omega-3 Trial (VITAL), which is a randomized, controlled study of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease.
Vitamin D may promote cell differentiation; inhibit cancer cell proliferation; and have antiinflammatory, proapoptotic, and antiangiogenic properties, says Dr. Manson and her colleagues. Data from laboratory studies and secondary analyses of small randomized trials suggest a protective effect for vitamin D against these diseases, but those studies are not enough to lead to recommendations. In 2011, the Institute of Medicine concluded that more data were needed to determine whether vitamin D lowers the risk of cancer and cardiovascular disease. “There are no large-scale, randomized trials of moderate to highdose vitamin D supplementation in the prevention of cancer,” says Dr. Manson. “It's critically important to be sure the benefits outweigh the risks, because correlation does not prove causation.”
VITAL has enrolled 20,000 participants across the country, including men aged 50 years and older and women aged 55 years and older. Participants will either receive 2000 IU/day of vitamin D or a placebo. Other participants in the study will receive both omega-3 and vitamin D or 2 placebos. And still another group will receive omega-3 and a placebo.
Many questions still need to be answered about these supplements, adds Dr. Manson. “More of a nutrient is not necessarily better,” she says. “Sometimes it can have a deleterious effect; for example, too much iron can be bad for the heart and liver.”
In addition to determining whether these supplements reduce the risk of total cancer and cardiovascular events, the study also will examine whether they reduce the risk of sitespecific cancers such as those of the colorectum, breast, and prostate. The mean treatment period will be for 5 years, with final results expected by 2017.
Hormone Receptor Status
Another recent study that demonstrated some benefit to certain foods with regard to cancer risk was published in January 2013 in the Journal of the National Cancer Institute.1 The study, led by Seungyoun Jung, ScD, of Brigham and Women's Hospital, found that although there is no association between total fruit and vegetable intake and the risk of overall breast cancer, there is an association between vegetable consumption and a reduced risk of estrogen receptor (ER)-negative breast cancer.
Dr. Jung and colleagues analyzed data from 20 cohort studies of women who were followed for a maximum of 11 to 20 years. They examined at the association between high and low intakes of fruits and vegetables and the risk of developing breast cancer in each study. They then generated summary estimates for all the studies combined.
The findings demonstrated a statistically significant link to a lower risk of ER-negative breast cancer, but not to ER-positive breast cancer. The lower risk was found to be associated mainly with higher vegetable consumption. “The reason underlying that observation is not clear, but it may be that bioreactive compounds are more concentrated in vegetables and may have more effect in ER-negative breast cancer,” Dr. Jung says. “I think it would be important to find mechanistic evidence to support our research.”
In an accompanying editorial in the same journal, however, Cynthia Thomson, PhD, and Patricia Thompson, PhD, of the Arizona Cancer Center in Tucson, write that the study findings should be approached with some caution.2 “Despite the robust findings of this pooled analysis of a very large set of prospective studies and nearly 1 million women, limitations in the selfreport of dietary measures is a well-recognized source of bias,” they write. They highlight the need for more strongly correlated biomarkers of vegetable and fruit exposure when evaluating these associations. Potential cofounders also may play a role in challenging these findings, including health behaviors such as physical activity, nonsmoking, and cancer screenings, they note.
Dr. Hoover concludes that although the new tools for dietary research are promising, scientists still do not have enough data to develop guidelines concerning specific foods and cancer risk. “Right now, given the increase in obesity, that is a major public health problem across the board,” he says, “but getting down to specific foods, we're not there yet.”