A Professor at The University of Alabama at Birmingham, Trygve Tollefsbol’s innovative research in aging, diet and cancer prevention stems from years of insights into turning genes “on” and “off.” The science of altering gene activity without changing the DNA is known as epigenetics, a burgeoning area of study for disease prevention. Now Tollefsbol’s research is yielding clues to genes important to both aging and cancer, such as genes involved with maintaining telomeres. (Telomeres are the DNA tips of our chromosomes, and shorter telomeres are linked with aging and cancer.) Tollefsbol, who presented his findings at AICR’s Research Conference, is beginning an AICR-supported study investigating how green tea may epigenetically prevent breast cancer from developing.
Q: Your lab studies show dietary compounds inhibit an enzyme that makes telomeres – called telomerase – but why doesn’t this also affect normal cells?
A: As we age, there is virtually no telomerase activity in normal cells. It’s downregulated [decreased] early on during development. That's when a molecular clock starts with aging and the telomeres first start shortening.
Q: Our cells start aging before we’re even born?
A: Yes, but that downregulation is a good thing because telomerase predisposes us to cancer. Cancer cells love telomerase; they are addicted to it. In 90 percent of cases, cancer cells need telomerase to multiply. We can target the cancer cells to inhibit [lower the level] telomerase and have essentially no effect on the normal cells because they do not have telomerase.
“Cancer cells love telomerase; they are addicted to it. In 90 percent of cases, cancer cells need telomerase to multiply. ”
Q: What’s the result of inhibiting telomerase?
A: If you inhibit telomerase, the telomeres of the cancer cells will shorten and the cells will die.
Q: How did you start working with dietary compounds?
A: Our lab had been studying aging, cancer and telomerase for many years; then several years ago I learned that other labs were finding a number of different dietary compounds that may have epigenetic effects. That’s an area we had been working on for quite a while so we thought we could help. We started looking at EGCG, (found in green tea), genistein (in soy) and sulforaphane (in cruciferous vegetables). We discovered that these compounds decreased telomerase levels through epigenetic control of the gene encoding telomerase, and we realized the importance of diet and cancer prevention.
Q: A lot of your research is in stopping pre-cancerous cells; these cells also need telomerase?
A: Yes. In general, as a cell becomes more and more cancerous and malignant the higher its telomerase activity, so pre-cancerous cells generally do have telomerase just not as much.
Q: You started working in epigenetics when the field was relatively young, how has it changed?
A: I first started studying epigenetics back when nobody thought it was important. It’s been quite a joy to watch the surge in this area in what was thought to be an esoteric field back then. Now we know that epigenetic processes are as or more important than genetic mutations in causing cancer. If you have a mutation in a gene and that’s causing cancer it may not be so easy to take a drug to inhibit that gene. But if you have these many different dietary compounds and they turn genes off or on it can really impact the genes involved in aging and cancer: that’s the real power and that can occur at any age.
A: We showed that glucose restriction extended the lifespan of normal human lung cells and it also prevented pre-cancerous cells from forming cancer. Both are very important. Many people view aging as a cellular process: if the cells live longer, chances are you will live longer.
Q: Was it the sugar or the fewer calories having the affect?
A: We don’t know. We need to try similar studies and try restriction of certain food groups, sugar then fat and protein. We are testing this – the glucose metabolism.
Q: What are you hoping to learn from your new AICR-supported study involving green tea?
A: We have the means to convert normal breast cells into cancer cells and this allows us to not only study the early epigenetic aberrations that occur during this process, but to also assess the impact of green tea (EGCG) in preventing those aberrations and the development of breast cancer. Also, this is a novel cancer prevention model system that we are hopeful will be useful for future studies of cancer prevention.
Excerpted from ScienceNow.
Single, young men at a healthy weight walk more than other groups of Americans, but in general, Americans are relatively inactive and walk far less than those in other countries.
In the study, about 1,100 adults completed an online survey and wore a pedometer for two days. Data was weighted to represent the U.S. population.
Overall, participants walked an average of 5,117 steps per day, far fewer than the Swiss, Australians, and Japanese, according to similar studies, the authors wrote. In general, men walked more than women (5,340 steps per day versus 4,912) and walking declined with age. People who were obese walked about 1,500 fewer steps per day than those who were not overweight or obese.
The amount people walked was unrelated to their environment – whether a city, suburb or rural – and eating habits.
Source: Bassett DR Jr, et al “Pedometer-measured physical activity and health behaviors in U.S. adults.” Med Sci Sports Exerc. 2010 Oct;42(10):1819-25.
African American women who eat at least two serving of vegetables daily are less likely to develop certain types of breast cancer than women with low vegetable intake, suggests a new study published in the American Journal of Epidemiology. The study is based on data from 59,000 African American women who are part of the Black Women's Health Study (BWHS).
At the start of the study, participants answered questions on their fruit and vegetable intake. After tracking the women’s health for 12 years, the authors linked total vegetable consumption to decreased risk of estrogen receptor-negative (ER)/progesterone receptor-negative (PR-) breast cancers. ER-/PR- breast cancers are less likely to respond to treatment and thus are associated with a higher mortality rate. The incidence of ER-/PR- breast cancer was 43 percent lower among women consuming at least two vegetables per day compared with women who ate fewer than four vegetables per week. There was no link between fruit intake and any type of breast cancer risk.
For individual vegetables and fruits, there was a trend toward those who consumed the highest amounts of cruciferous vegetables and carrots with lower overall breast cancer risk.
Source: Boggs DA, et al. “Fruit and Vegetable Intake in Relation to Risk of Breast Cancer in the Black Women's Health Study.” Am J Epidemiol. 2010 Oct 11.
A small but emerging area of research on sedentary behavior shows that being sedentary for long periods time appears to increase the risk for several cancers. The review article, published in the October issue of Cancer Epidemiology Biomarkers & Prevention, also offers several biological explanations as to how sedentary behavior may increase cancer risk.
In research, the term sedentary behavior refers to prolonged sitting or lying down, and it is often measured by time spent watching TV or videos, and sitting time. The review identified 18 studies on sedentary behavior and cancer risk, and 10 of the studies found a link. Sedentary behavior was linked with increased colorectal, endometrial, ovarian, and prostate cancer risk; cancer mortality in women; and weight gain in colorectal cancer survivors.
Sitting for long periods of time may lead to cancer development in several ways, the studies suggest, with the most consistent evidence pointing towards excess body fat. (AICR’s expert report and its updates found that sedentary living increased the risk of excess body fat, which is one cause of seven types of cancer.) Studies also suggest sedentary behavior may lead toward metabolic disorders and inflammation, which also increase the risk of cancer.
Right now, more research is needed to understand the links and mechanisms of sedentary behavior to cancer risk, note the authors. But given that sedentary behavior is ubiquitous, focusing on reducing this behavior may be one strategy to improve health behavior in general.
Source: Lynch BM. “Sedentary Behavior and Cancer: A Systematic Review of the Literature and Proposed Biological Mechanisms.” Cancer Epidemiol Biomarkers Prev. 2010 Oct 26. [Epub ahead of print]
The rarity of cancer in the study of disease among Egyptian mummies supports the evidence that diet and other modern environmental factors play a major role in the disease, suggests a new study published in Nature Reviews Cancer. The researchers analyzed mummified remains and ancient literature to search for signs of cancer.
Among tens of thousands of skeletons, studies have only found a few diagnoses of possible and/or probable malignancies, say the authors. Studies carried out on hundreds of mummies from sites across the world have only identified a handful of cancer diagnoses. And while there are descriptions of cancer in ancient literature, references to the disease are rare.
One argument as to why ancient Egyptians did not develop cancer points to their relatively short lifespan. In fact, the researchers say, evidence shows that the average lifespan of the wealthy class was between the ages of 40 and 50 years, while others died between the ages of 25 to 30. Many individuals did live to the age to develop other degenerative disease, such as arthritis. Also, the authors say, bone tumors primarily affect the young so a similar pattern would be expected in ancient populations. The authors conclude that the evidence combined, points to the role of modern, environmental factors.
Source: A. Rosalie David and Michael R. Zimmerman.” Cancer: an old disease, a new disease or something in between?” Nat Rev Cancer. 2010 Oct;10(10):728-33.