Monday, November 10, 2008

American Institute for Cancer Research Annual Meeting Highlights

Researchers Focus on the New Science of Epigenetics

A panel of leading scientists presented promising research involving the new science of epigenetics and cancer development.

Epigenetics refers to any alterations in how our genes get translated (or expressed) that do not involve direct changes to the DNA itself. In recent years, scientists have discovered that environmental factors, such as the foods we eat, can spur epigenetic changes. In effect, diet can activate or silence the expression of genes that play a role in the development and progression of cancer.

AICR’s 2007 expert report found that diets containing certain foods can either increase or decrease the risk of cancer. The science of epigenetics may help explain why.

The opening session of AICR’s conference, Food, Nutrition, Physical Activity and Cancer, held in Washington, DC, focused on the emerging research relating to diet, epigenetics, and cancer.

Genes, Diet and Skin Cancer

Richard L. Eckert, PhD, chair of the Department of Biochemistry & Molecular Biology at the University of Maryland School of Medicine, chaired the session. He also presented his lab’s research showing that the major compound in green tea led to epigenetic changes that effects the expression of a group of genes involved in skin cancer. The findings suggest that dietary compounds can help prevent cancer by influencing how genes work, said Dr. Eckert.

Inheriting Epigenetic Changes

David IK Martin, MD, a scientist at the Children’s Hospital Oakland Research Institute in Oakland, Calif., presented research on passing down epigenetic changes from parent to progeny. Dr. Martin’s mice studies have demonstrated that a mother’s diet during pregnancy shifted the expression of cancer-related genes in her grandchildren. He presented research on the questions and possible mechanisms involved with retaining epigenetic changes over generations.

Foods Reversing Epigenetic Cancer Cell Growth

The growth of cancer is linked with a group of proteins in the body that epigenetically silences genes relating to natural, programmed cell death. Roderick H. Dashwood, PhD, a researcher at the Linus Pauling Institute in Oregon, presented evidence showing how natural compounds found in foods such as broccoli and garlic can interfere with the actions of this protein group and restore natural cell death. He discussed his lab studies showing how these dietary compounds suppressed tumors and inhibited the group of protein’s activity.

Behind a Vitamin’s Epigenetic Effects

From the University of Nebraska at Lincoln, Janos Zempleni, PhD, Associate Professor of Molecular Nutrition, explained his research demonstrating one way in which a B vitamin can lead to epigenetic changes. In both human and mouse cell studies, the vitamin biotin affected the actions of moveable chunks of DNA, which make up about half of the human genome. Because these moveable sequences of DNA relate to increased disease risk, said Dr. Zempleni, understanding how diet has an epigenetic effect on the DNA can reduce cancer risk.

Epigenetic Changes and Folate

Scientists have long known that folate and folic acid, the synthetic form of the B vitamin folate, produce epigenetic changes. Young-In Kim, MD, a researcher at the University of Toronto in Ontario and a leading expert on the topic, presented the latest findings on what is known about how and when folate alters DNA. When and for how long people take folic acid appears to play a key role in the epigenetic effects of the B vitamin, said Dr. Kim.

Cancer Experts Debate Vitamin D, Sunlight and Risk

The association between vitamin D and cancer risk is one of the most studied, most complex and most controversial issues in nutrition science. A panel of vitamin D experts weighed in, and presented evidence that sought to provide some clarity.

The panel on vitamin D and cancer was part of the 2008 Annual Research Conference on Food, Nutrition, Physical Activity and Cancer, presented by the American Institute for Cancer Research (AICR) in Washington, DC.

How Much Sunlight?

Experts seeking to offer the public advice must weigh the fact that vitamin D is produced in skin exposed to sunlight against the clear risks of skin cancer caused by excessive exposure to UV rays, said Mary Frances Picciano, PhD, of the Office of Dietary Supplements at the National Institutes of Health. She noted that, as yet, no optimal level of sun exposure has been determined that poses no or little risk of skin cancer.

Some experts have proposed that the current definition of vitamin D deficiency is too low, and the US government is now considering raising the recommended intake for vitamin D. But Picciano noted that significant questions remain. More work, for example, must be done to ensure measurement of vitamin D blood levels is both accurate and consistent.

Vitamin D Deficiency Implicated in African American Cancer Rates

Lisa B. Signorello, ScD, of Vanderbilt University and the International Epidemiology Institute pointed out that many of the cancers linked to vitamin D deficiency are more prevalent among African Americans.

The high concentration of melanin in the skin of African Americans blocks the formation of vitamin D. Signorello also presented data suggesting that African Americans consume fewer foods that have been fortified with vitamin D. She suggested that this combination of lower vitamin D production and lower dietary intake may be a key factor in higher rates of some cancers among African Americans, and proposed that targeted efforts to increase vitamin D status may be an important means to prevent cancer in this group.

Two Clues to How and Why Vitamin D Seems Protective

The body produces a biologically active from of vitamin D that has been associated with anticancer effects in the lab and in epidemiological studies. John White, PhD, of McGill University presented data that may help explain why. His group found that the vitamin D receptor stimulates proteins that are involved with regulating the cell cycle and that also “turn on” tumor suppressor genes.

Another researcher presented evidence linking vitamin D to lower risk of skin cancer. Daniel Bikle, MD, PhD, and his colleagues at the University of California at San Francisco have demonstrated that animals that lack the receptor for vitamin D are more likely to develop skin cancer when exposed to UV rays.

He hypothesizes that the vitamin D receptor regulates two protective biochemical pathways in skin cells. When this receptor is not present, these pathways get disrupted in ways that make skin cancer more likely.

His findings suggest that very brief exposure to sunlight – 10 to 15 minutes, in his animal model – may stimulate the vitamin D receptor, activate those two pathways, and actually be protective against skin cancer, Dr. Bikle said. If borne out in human investigations, his research will represent a substantial contribution to the ongoing scientific discussion about optimal vitamin D levels and sunlight exposure.

Newly Discovered Gene Plays Early Protective Role

Stephen Byers, PhD, of Georgetown University, presented evidence on a newly identified gene called TIG1, which researchers suspect has the potential to suppress tumors.

Using normal human prostate cells, Dr. Byers and his colleagues found that this gene is indeed able to suppress an early stage of tumor development when exposed to vitamin D and a derivative of vitamin A called retinoic acid.

The Emerging Science of Personalized Diets for Cancer Prevention

Researchers discussed the impact of diet in helping to grow “healthy” bacteria in the human gut, which emerging evidence suggests may influence how other dietary constituents are utilized for cancer protection. The evidence for inclusion of probiotics (foods and supplements containing healthy bacteria) in the diet for lower cancer risk was discussed as well as potential mechanisms. Researchers also touched upon the impact that individual genetic variations may have on the effectiveness of the bacterial response to certain foods.

In addition, researchers noted that genetic differences among individuals also affect how certain foods and nutrients combat the cancer process. The future of a personalized approach to eating for increased cancer prevention was anticipated.

Beneficial Bacteria May Play a Role in Colon Cancer Prevention

While the role of probiotics in colon cancer prevention has been studied extensively in laboratory studies, there are far fewer interventions with human subjects and the results remain inconclusive, if not directly contradictory. Joseph J. Rafter, PhD, professor of medical nutrition at the Karolinska Institutet, Stockholm, Sweden, presented a summary of the laboratory evidence today, along with a report on a recently completed human intervention trial. Dr. Rafter discussed the potential mechanisms by which probiotic bacteria may inhibit colon cancer development and called for more studies in humans to help inform the current discussion.

What’s In Your Gut: Individual Responses to Microflora

The activity of microorganisms in the human gut can directly influence cancer risk, according to Johanna W. Lampe, PhD, RD, of the Fred Hutchinson Cancer Research Center in Seattle. Bacteria in the gut play a role in the uptake of beneficial dietary components (phytochemicals, for example) and can help neutralize dietary toxins, she said. What you eat impacts the growth and type of intestinal flora in your digestive tract and individuals have genetic variations that can impact how our bacteria impact our personal cancer susceptibility.

A Tailored Approach to What’s on Your Plate

From the Center for Cancer Prevention Research at Rutgers University, Ah-Ng Tony Kong, PhD, presented an overview of the role of personalized genomics in nutrition and cancer prevention. Dr. Kong highlighted several animal studies to suggest how phytochemicals in foods may directly influence certain defensive enzymes and protect against cellular damage. He discussed how advances in science might soon enable individuals to customize their diets to better protect against cancer by understanding their own genetic profile.

Eating According to Science

Steven H. Zeisel, MD, PhD., professor and chair of the Department of Nutrition at the University of North Carolina offered evidence that what we eat can alter the expression of certain genes that impact cancer risk. Dr. Zeisel highlighted choline and folate in particular and discussed how early intake of certain dietary constituents may account for differences in cancer risk later in life.

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