Photo by Todd Mcnaught
Besides the obvious health benefits of good nutrition, eating smart may be an important step toward preventing cancer. Yet the variety of foods in the average diet makes it difficult to definitively associate a specific dietary component with cancer risk. To complicate matters further, many experts believe that subtle genetic differences in individual metabolism may be links to cancer prevention.
That's why many scientists now use blood, DNA and tissue samples from large study populations to better understand the connection between diet and cancer risk, says Dr. Ulrike (Riki) Peters, a new faculty member in the Cancer Prevention Research Program of the Public Health Sciences Division.
This important link between population studies and lab-based analysis enforces the need for collaborations among multi-disciplinary teams of researchers. Peters' own work in the field focuses on integrating genetic and molecular methods to better understand the role of selenium, vitamin D, calcium and other dietary components in the prevention of prostate and colorectal cancer. Peters views Fred Hutchinson as an ideal place for studying the nutritional and genetic contributions to disease development.
"The center provides incredible resources," she said. "Most important are the excellent colleagues and their openness to collaboration. You can find experts in all cancer-related disciplines.
"Furthermore, many large and well-designed population-based studies—which are crucial for conducting nutritional epidemiological research—are ongoing at the center," she said. "There are very few research institutes in the country with comparable resources."
"Riki has a lot of natural ties with folks here," said Dr. Alan Kristal, a nutritional epidemiologist in the Cancer Prevention Research Program. Her strong interest in investigating colorectal and prostate cancer makes her a particularly good fit with center investigators, he said.
The gene-diet connection
Peters plans to foster new collaborations with center faculty to further research that she began while at the National Cancer Institute (NCI). Working on the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, Peters and teams of investigators studied the role of dietary factors such as selenium in prostate and colorectal cancer risk.
Normally acquired from several food sources, including grains, bread, eggs, meat and fish, selenium can also be given in dietary supplements. Selenium plays a key role in activating a small number of enzymes termed selenoenzymes. Many selenoenzymes protect cells against oxidative stress-a process potentially causing DNA damage, which can lead to cancer.
People vary in their genetic code: such subtle differences in the gene sequence—termed genetic variation—can affect the activity of seleno-enzymes. Together with colleagues at the NCI and Johns Hopkins University, Peters analyzed the genetic code of about 100 individuals to determine the location of common variations (polymorphisms) in genes encoding selenoenzymes, allowing her to reconstruct the inherited pattern (haplotype structure).
"We are currently investigating if genetic variations in selenoenzymes are associated with risk for prostate cancer," she said. "We are further studying if these genetic variations alter the association between selenium intake and prostate cancer risk."
At the center, Peters plans to explore whether genetic variation in selenoenzymes relates to differences in the activity of these enzymes and affects oxidative stress. This research may lead to a better understanding of whether selenium's role in combating oxidative stress contributes to cancer prevention.
Further, Peters plans to investigate if certain genetic variations modify how individuals respond to selenium supplementation by comparing participants receiving dietary supplements to those who are not.
Increasingly, epidemiological studies collect tissue samples that provide excellent opportunities to study the effects of selenium and other dietary factors at the tissue level in a population-based setting, she said.
Selenium represents only one aspect of Peters' research. Her experience at the NCI provided her with a wealth of collaborative projects, giving her broad-based experience in nutritional epidemiology. Incorporating molecular and genetic approaches, she has also studied vitamin D and calcium in the prevention of colon cancer, the second leading cause of cancer death in the United States, according to statistics published by the NCI.
Increasing evidence suggests that both vitamin D and calcium are related to lower risk of colon cancer. Calcium, for example, may bind fatty acids and secondary bile acids in the colon. If not bound, these potentially carcinogenic components could lead to tumor development.
Nutrients and colorectal-cancer risk
Vitamin D may inhibit tumor growth by affecting cell cycle control. Vitamin D may also act together with calcium to prevent colon cancer since vitamin D tightly regulates blood calcium levels. However, the mechanism of their concerted action remains unclear.
"We want to explore a possible link between vitamin D, calcium and cancer further," Peters said.
As with selenoproteins, Peters is interested in exploring this connection by investigating variants in genes related to vitamin D and calcium. One important player may be the calcium-sensing receptor, a protein that sits on the surface of colon cells and senses elevated calcium levels in both the blood stream and the colon. Calcium-sensing receptors respond to increasing calcium levels by send-ing signals into the cell that inhibit tumor growth.
Vitamin D regulates the calcium-sensing receptor, prompting Peters and NCI colleagues to further explore this possible link between vitamin D and calcium in preventing colon cancer. She found that some calcium-sensing receptor gene variants were, in fact, associated with a lower risk for developing colorectal adenoma, a precursor lesion for colorectal cancer.
A native of Germany, Peters received her Ph.D. in nutrition at the University of Kiel, and came to the U.S. to study epidemiology at the University of North Carolina at Chapel Hill before moving to the NCI. Throughout her many research collaborations in these institutes, gathering meaningful data relating dietary components to cancer risk has required teamwork and a diversity of expertise and resources.
"In my experience, when I am working together with researchers from different disciplines, the research became more innovative," she said.
"I think that is the direction epidemiology will continue to go in the future."
[Danielle Ippolito is a pharmacology graduate student at the University of Washington.]