National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
November 15, 2011 • Volume 8 / Number 22
Special Issue: Cancer and Obesity Research

COMMENTARY

Dr. Rachel Ballard-Barbash

The Emerging Evidence about the Role of Obesity in Cancer
by Dr. Rachel Ballard-Barbash

Concern about the public-health consequences of obesity has risen as its prevalence has increased worldwide. Obesity rates have more than doubled since 1980, according to the World Health Organization.

In the United States alone, the 2007–2008 National Health and Nutrition Examination Survey results show that 34.2 percent of adults 20 years of age or older are overweight, 33.8 percent are obese, and 5.7 percent are extremely obese. In 1988–1994, in contrast, only 22.9 percent of adults were obese. Read more > >

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    • State-of-the-Science Conference on Active Surveillance for Prostate Cancer Slated for December


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Guest Commentary by Dr. Rachel Ballard-Barbash

The Emerging Evidence about the Role of Obesity in Cancer

Dr. Rachel Ballard-Barbash Dr. Rachel Ballard-Barbash

Concern about the public-health consequences of obesity has risen as its prevalence has increased worldwide. Obesity rates have more than doubled since 1980, according to the World Health Organization. In the United States alone, the 2007–2008 National Health and Nutrition Examination Survey results show that 34.2 percent of adults 20 years of age or older are overweight, 33.8 percent are obese, and 5.7 percent are extremely obese. In 1988–1994, in contrast, only 22.9 percent of adults were obese.

A recent NIH research initiative, based on simulation modeling, estimated the public health and economic consequences of the continued rise in obesity among the aging populations of the United States and the United Kingdom. The researchers found that, by 2030, 65 million more U.S. residents will be obese, and that this increase will carry associated costs of $48 to $66 billion per year for treating obesity-related diseases. Clearly, the costs of obesity are substantial and increasing rapidly.

Many people are familiar with the evidence that obesity increases the burden of common chronic diseases such as diabetes, cardiovascular disease, asthma, and arthritis. Surprisingly, despite decades of research indicating a strong association between obesity and cancer incidence and prognosis, obesity's contribution to cancer has been widely recognized only recently. 

Before effective cancer screening and treatments were commonly available, many people were not diagnosed until their cancer was advanced, when they may have already experienced weight loss and cachexia. In addition, patients undergoing cancer treatment often experienced significant nausea and vomiting, which led to further weight loss. Cancer was thus considered to be associated with weight loss, rather than with obesity. 

Defining Obesity

To measure obesity, researchers commonly use a scale known as the body mass index (BMI). BMI is calculated by dividing a person's weight in kilograms by his or her height in meters squared. BMI provides a more accurate measure of obesity than weight alone.

NIH guidelines place adults 20 years of age and older into the following categories based on their BMI:

BMICategory

Below 18.5

underweight

18.5 to 24.9healthy
25.0 to 29.9overweight
30.0 and aboveobese

For children and adolescents under 20 years of age, the definitions of overweight and obesity are based on the Centers for Disease Control and Prevention's BMI-for-age growth charts

BMI-for-age at or above sex-specific 85th percentile, but less than 95th percentileOverweight
BMI-for-age at or above sex-specific 95th percentileObese

Research during the 1970s in animal models and epidemiologic studies examining factors influencing breast cancer began to suggest, however, that higher body mass index (BMI) ratings increased the risk of breast cancer. Since then, extensive research at the basic, clinical, and population levels by investigators around the world has shown that obesity is associated with an increased risk of cancers of the endometrium, postmenopausal breast, gastrointestinal tract (colon, pancreas, adenocarcinoma of the esophagus, and gallbladder), kidney, and thyroid, as well as aggressive forms of prostate cancer. Adult weight gain and increased amounts of abdominal body fat have also been associated with increased risk for several cancers.

During the last two decades, an extensive body of research has begun to identify an association between obesity and worse prognosis and outcomes among some cancer patients, particularly those with breast, prostate, and colon cancer. In interpreting the research on cancer risk and prognosis, it is important to understand that obesity is associated with physical inactivity and poor dietary practices that may also increase the risk for cancer.

Researchers are exploring the many potential mechanisms by which obesity may influence cancer risk and prognosis. Early research focused on the effect of obesity on adverse changes in sex hormones such as estrogens and androgens, particularly during puberty, pregnancy, and menopause.

More recent research has examined mechanisms related to insulin and related growth factors, adipokines (cytokines secreted by fat tissue), other metabolic and growth factors, inflammatory factors, altered immune response, and oxidative stress, relative to all phases of cellular growth and cell death. Researchers are also looking at the effects of obesity and of energy expenditure and intake—at the cellular and whole-body level—on many other mechanisms that may influence cancer. Other research indicates that sleep, alterations in circadian rhythms, and changes in the microbiome may also influence obesity and cancer.

Although important findings have already been made about the links between obesity and cancer, much research remains to be done in a number of areas. For example, relatively few studies of obesity and cancer risk have adjusted for the potential effects of physical activity; more have adjusted for dietary factors that may influence cancer risk, such as total calories or amount and types of dietary fat consumed. In addition, no clinical research to date has examined the effect of weight loss on the initial development of cancer; nor have clinical trials been funded to test the effect of weight loss on the likelihood of dying from cancer once diagnosed. 

This special issue of the NCI Cancer Bulletin explores how NCI is supporting extensive research at the cellular, animal, and clinical levels to address these gaps in our knowledge about the role of obesity in cancer. NCI's initiatives include partnerships with institutes across NIH, that seek to advance research to understand the environmental, policy, and social forces that may be contributing to the worldwide obesity epidemic. 

For example, given the substantial evidence showing how difficult it is to reverse obesity once it occurs, much research is focused on obesity prevention in children, families, and the communities in which they live, play, and work. NCI is working with its partners at NIH, the U.S. Department of Agriculture, the Centers for Disease Control and Prevention, and the Robert Wood Johnson Foundation on the National Collaborative on Childhood Obesity Research. This initiative seeks to enhance the implementation and effectiveness of research to identify multilevel individual, social, environmental, and policy factors that may help to reverse the rising trends in childhood obesity, particularly among populations that are at the greatest risk of obesity and its adverse consequences.

Obesity prevention efforts, such as the Let's Move campaign, are also important, not just because they seek to help control childhood obesity, but because they may also reduce cancer-related morbidity and mortality in the United States.

Dr. Rachel Ballard-Barbash
Associate Director, Applied Research Program
NCI Division of Cancer Control and Population Science

Special Issue: Cancer and Obesity Research

Uncovering the Mechanisms Linking Obesity and Cancer Risk

Being overweight or obese is associated with an increased risk for many types of cancer, including postmenopausal breast cancer; endometrial cancer; and colorectal, esophageal, gallbladder, kidney, pancreatic, and thyroid cancer. These risks are not minor. In 2002, the International Agency for Research on Cancer, using European data, estimated that obesity contributed to more than one-third of endometrial and esophageal cancer cases and a quarter of kidney cancer cases. (See the table below.)

Being overweight or obese also raises the risk of dying of cancer. In an often-cited paper published in 2003 in the New England Journal of Medicine, researchers from the American Cancer Society estimated that 14 percent of all cancer deaths in men and 20 percent in women could be blamed on excess weight.

Type of CancerEstimated Percentage Caused by Obesity

Endometrial

39

Esophageal37
Kidney25
Colon11
Postmenopausal Breast9
Source: Weight Control and Physical Activity, International Agency for Research on Cancer.

The obvious question is: Why? What biological processes mediate the relationship between excess body fat and increased cancer risk? Researchers are only beginning to tease out the answers, but almost all the factors under study are rooted in the fact that adipose (fat storage) tissue is highly metabolically active. Once thought to be just a passive storage depot for fuel, adipose tissue is now known to pump out an astounding array of hormones, growth factors, and signaling molecules, all of which can influence the behavior of other cells in the body.

Excess Hormones, Extra Risk

Most, if not all, of the molecules being studied as potential mediators between obesity and cancer are not cancer-causing but cancer-promoting. That is, they do not cause the mutations that turn a normal cell into a cancerous cell, but instead feed the growth and proliferation of malignant cells.

One of the best understood of the pathways that may lead from obesity to cancer involves the hormone estrogen, which fuels a large number of breast and endometrial cancers. In postmenopausal women, the levels of estrogen circulating in the bloodstream normally drop drastically, as the ovaries stop producing the hormone.

But fat tissue also produces estrogen, through a cellular pathway involving the enzyme aromatase, the target of several breast cancer therapies called aromatase inhibitors. In obese women, "the body fat just becomes an estrogen-producing machine," explained Dr. Leslie Bernstein, director of the Division of Cancer Etiology at City of Hope Comprehensive Cancer Center, who has studied the relationship between estrogen and cancer risk for years through the California Teachers Study.

This excess estrogen produced by fat can feed cancer cells that express the estrogen receptor. But estrogen alone does not account for all of the extra risk for these cancers in obese postmenopausal women. Another likely player in many types of cancer, including breast, colorectal, and pancreatic cancer, is insulin, the hormone that triggers cells in the body to take up glucose (sugar) from the bloodstream.

Woman checking blood sugarObesity often goes hand in hand with type II diabetes and insulin resistance, which may contribute to cancer risk.

Obesity often goes hand in hand with metabolic syndrome and type II diabetes. In type II diabetes, the body's cells stop responding to insulin, causing a buildup of glucose in the blood, which in turn stimulates the body to produce even more insulin. And in some cancers, "insulin acts as a mitogen—it makes cancers grow faster," said Dr. Michael Pollak, director of the Division of Cancer Prevention at McGill University in Montreal.

Interestingly, a diabetes drug called metformin, which lowers the levels of blood glucose, has shown some anticancer activity. Several studies have suggested that people with diabetes who took metformin had a lower risk of developing cancer or dying from the disease compared with diabetics who did not take metformin. Currently, several clinical trials, including one in breast cancer, are testing the addition of metformin to standard treatment.

It will be important, stressed Dr. Pollak, to continue basic science research on metformin, given the many unanswered questions about who should take the drug. "I think this is an extremely promising area of cancer research, but we need to do more basic science research before we'll be able to design the best clinical trials" to figure out which patients are most likely to benefit from the drug, he said.

For example, other diabetes drugs lower insulin levels but don't show a similar anticancer effect, suggesting that metformin may affect more than just the insulin pathway. Also, some patients' tumors have mutations in the insulin signaling pathway that make the cells act as if extra insulin is always present, even when it's not. In these cases, reducing insulin would be futile in terms of cancer control. "So maybe those patients shouldn't be on clinical trials of metformin," said Dr. Pollak.

Digging Deeper

A myriad of other molecules are being studied to see if they contribute to the relationship between obesity and cancer. Some of these molecules, such as certain interleukins, are part of the body's natural inflammatory response, which is often chronically overstimulated in people who are obese. Others are signaling molecules called adipokines (cytokines produced by fat tissue), levels of which can be affected by weight gain.

Within NCI, researchers in the Division of Cancer Epidemiology and Genetics (DCEG) are using several multimarker panels to study molecular pathways that may link obesity to cancer risk in humans. Two panels—one that assesses 15 different estrogens and estrogen metabolites, and one that assesses 79 molecular markers of inflammation—are already being used to examine these mechanisms.

A third, more experimental panel simultaneously tests 400 to 600 small molecules to give a snapshot of metabolism at the time of sample collection, said Dr. Steve Moore, a research fellow in DCEG's Nutrition Epidemiology Branch. With these panels, "you can look at how the markers are related to cancer risk, you can look at how obesity is related to cancer risk, and you can look at how obesity is related to cancer risk after adjusting for the marker levels," explained Dr. Moore. "So by triangulating these three things, you can estimate which molecular mechanisms obesity is most likely to act through."

Other researchers are examining genetic variants that might also influence how obesity and cancer risk intersect. "A lot of people have looked at biomarkers like insulin, but what are the [full] genetic and molecular pathways being affected by obesity?" asked Dr. Li Li, associate director for Prevention Research at Case Comprehensive Cancer Center, Case Western Reserve University. His project, supported by the first tranche of Transdisciplinary Research on Energetics and Cancer (TREC) funding, is looking at how genetic variants found naturally in the population influence whether obesity can promote colon polyp formation.

All of this research may eventually help create targeted cancer prevention measures and treatments for overweight and obese patients, based on a better understanding of the molecular events driving progression. For now, "I would say what we know now supports the adoption of a healthier lifestyle that promotes weight control," concluded Dr. Moore.

Sharon Reynolds

Special Issue: Cancer and Obesity Research

Searching for Clues to Obesity among the Body's Many Microbes

Diagram showing human microbial communities studied by the Human Microbiome Project Researchers are examining the microbial communities found at several different sites on and in the human body to analyze the role of these microbes in human health and disease.

The human body contains ten times as many microbial cells as human cells. Most of the time, these microbes are our partners in health, contributing to a strong immune system and the digestion of dietary components to produce essential nutrients, among many other roles. But growing evidence indicates that, under certain conditions, some of these microbes may worsen our health and increase the risk of disease.

Using new genomic tools, researchers have been systematically identifying many of the microbes living in and on our bodies. The NIH-led Human Microbiome Project, for instance, has been characterizing the communities of microbes, or microbiota, at five body sites—the gut, skin, mouth, nose, and vagina. (Collections of microbial genes are known as microbiomes.)

Having developed the tools and information to study these microbial ecosystems, researchers are shifting from asking "Who is there?" to "What are they doing?" The goal is to learn how microbes help maintain human health or set the stage for disease. Early efforts in this area have linked microbes in the gut to obesity, which is a risk factor for cancer.

"We are learning a lot about the microbes in the gut and about associations with obesity," said Dr. James Goedert of NCI's Division of Cancer Epidemiology and Genetics (DCEG). "It is too soon to say whether changes to the microbiota play a causal role in obesity. We also need to explore how these associations relate to cancer."

Harvesting Energy for Humans

Research suggests that communities of microbes in the gut influence—or are influenced by—diet. Researchers have long known that microbes digest foods that humans cannot, thereby supplying nutrients that humans need. Gut bacteria produce energy for the body by fermenting plant polysaccharides and dietary fiber, for example.

"How much energy is harvested from the human diet is directly influenced by the type of bacteria we house in our colons," explained Phil Daschner of NCI's Division of Cancer Biology, who co-led a recent NCI meeting on the human microbiome and cancer. "It's not just what you eat, but also which bacteria you have in the gut that are breaking down what you eat," he added.

If different configurations of gut microbes are found to be associated with a lower risk of certain diseases, then it may be possible to prevent—or even treat—these diseases simply by modifying microbial communities.

Finding out the molecular mechanisms by which these bacteria are signaling their effects in the human host is critical for developing disease prevention and treatment strategies.

—Phil Daschner

Daschner and others believe that to achieve this goal it will be important to understand how bacteria might be affecting the body. "Finding out the molecular mechanisms by which these bacteria are signaling their effects in the human host is critical for developing disease prevention and treatment strategies," he said.

Nonetheless, interest in the gut microbiome and obesity has grown, in part because of research led by Dr. Jeffrey Gordon at the Washington University School of Medicine in St. Louis. In one study, his research team transplanted certain bacteria from the guts of obese mice into the guts of germ-free mice. These animals subsequently became obese themselves.

A second study involved sets of human twins and their mothers. The researchers found differences in the fecal microbiota of lean twins compared with obese twins; notably, obesity was associated with decreased diversity of gut microbes. In addition, the activity of microbial genes involved in several aspects of nutrient metabolism also differed between the two groups.

The Complexity of Microbiota

"We are just beginning the journey of looking at the configurations of different gut communities in people of different ages living under distinct cultural conditions," Dr. Gordon said in a recent podcast discussing his research. The extent to which the configurations of these communities vary "is still an open question," he noted.

Probing the Oral Microbiome

In the coming months, NCI will be sending DNA samples from patients with oral cancer to Drs. Richard Hayes and Zhiheng Pei of New York University Medical Center. But rather than studying the human DNA in these samples, the researchers will be sequencing microbial DNA to explore associations between the mouth microbiome and cancer.

The study subjects were participants in a large NCI-sponsored cancer prevention trial. They were free of cancer when they joined the trial between 2000 and 2005; each person provided a DNA sample when they entered the study using an oral rinse they did at home and sent through the mail.

The samples, which arrived at NCI and were stored for later research, captured the DNA of microbes in each donor's mouth. As prediagnostic DNA samples, the specimens present a rare opportunity to study the oral microbiome before cancer symptoms appeared.

"By studying the microbiome, we have an opportunity to identify new bacterial agents that may cause cancer," said Dr. Pei. "The microbiome has given us a new target."

But he believes that studying the structures and functions of microbial communities could lead to a better understanding of the nutritional needs of humans. This work could also yield clues about the role of microbial ecosystems in obesity and malnutrition.

Although the role of the microbiome in cancer is even less clear than it is in obesity, several reports have suggested that certain microbiota have either a protective or a cancer-promoting role. "To me, this is an indication of the complexity of the microbiota," said Dr. Eugene Chang, who studies the gut microbiome and gastrointestinal diseases at the University of Chicago.

"Many of us believe," he continued, "that our collective microbiome in the human population is changing and that this is altering the critical host-microbiome interactions that determine our biology."

In a recent commentary, Dr. Chang urged the field to undertake studies of the mechanisms underlying these interactions. He also cautioned against "overzealous claims" about the significance of the findings based on current evidence. For example, one challenge will be to move beyond small studies that describe associations between changes in microbiota and health effects. Most of these studies are based on a single point in time and cannot show cause and effect.  

"We still haven't answered the initial questions we set out for the Human Microbiome Project: Why is the microbiome important to our health and what role does it have in disease?" Dr. Chang said.

"To answer these exciting questions we need large, well-designed studies that collect samples and that follow individuals over time to see which microbial differences are predictive of cancers and other diseases," said Dr. Mahboobeh Safaeian, an investigator with DCEG's Infections and Immunoepidemiology Branch. "Establishing a timeline of events will be important."

Exploring a New Frontier

A prospective study of the gut microbiota in the Amish, now under way, could yield clues to help answer a number of current questions. The study, led by Dr. Claire Fraser-Liggett of the University of Maryland School of Medicine, will evaluate the gut microbiota in lean and obese individuals over time, including before and after an experimental intervention.

This work and similar studies will almost certainly raise new questions as well as answer others. But the science is moving rapidly, and researchers are optimistic. "Things are happening so fast in this field—both scientifically and technically," said Dr. Goedert. Within a few years, the current research methods and tools could well be seen as obsolete, he added.

Dr. Chang agreed. "This field is like a frontier right now, and that's the appeal," he said. "We don't have signposts to tell us where to go."

Edward R. Winstead

Testing the Health Effects of Yogurt

In a two-track study involving humans and animal models, Dr. Gordon and his colleagues recently tested the effects of yogurt on the gut microbiomes of identical twins and mice with "humanized" microbiota. 

The researchers took fecal samples from the subjects during the 4 weeks before they ate the yogurt, the 7 weeks while they ate the yogurt, and another 4 weeks after they stopped eating the yogurt. Over this 4-month period, the diet appeared to have no substantial effect on the composition of the fecal microbiome. But the diet did cause changes in the expression of some microbial genes, resulting in alterations in metabolites that were detected in urine.

"This study demonstrated that a dietary intervention could exert a systemic effect. It is interesting that the population of microbes didn't change, but their activity did," commented Dr. Goedert.

The findings in the mice mirrored those in humans, suggesting that this strategy could be used more broadly to identify the effects of consuming foods containing live bacteria. "We can basically do global surveys at the intersection between what somebody eats and the response of their different microbes," Dr. Gordon explained in a recent podcast.

Special Issue: Cancer and Obesity Research

Bridging Disciplines to Study Possible Cancer-Obesity Links

Woman lifting weightsThe WISER Survivor trial at the University of Pennsylvania TREC center will test the effects of exercise and weight loss on biomarkers for cancer recurrence, quality of life, and lymphedema in overweight breast cancer survivors.

When it comes to understanding the connections between obesity and cancer, one thing is clear: It's complicated. In an effort designed to address this complexity, NCI launched the Transdisciplinary Research on Energetics and Cancer (TREC) initiative in 2005. TREC is a multicenter program that brings together investigators from diverse disciplines, ranging from biochemistry and molecular biology to behavioral science and urban planning, to understand the obesity-cancer link.

"The TREC initiative challenged the research community to look at this problem from a very different approach and to broaden scientific partnerships in a truly transdisciplinary way," said Dr. Linda Nebeling of NCI's Division of Cancer Control and Population Sciences, who oversees the TREC program.

Transdisciplinary research emphasizes collaboration, information sharing, and integration across academic areas to achieve a common goal. For TREC, the ultimate goal is to reduce the incidence of cancers that are linked to obesity, poor diet, and low levels of physical activity, as well as to improve the length and quality of life for cancer survivors.

In 2005, NCI awarded 5-year grants to the first four TREC research centers and a coordination center. This June, NCI announced funding of four new TREC research centers and continuation of the coordination center, which is located at the Fred Hutchinson Cancer Research Center in Seattle.

The coordination center "serves as the communication and infrastructure hub for TREC," said the center's director, Dr. Mark Thornquist. The center also promotes and facilitates data sharing among TREC investigators and with the broader scientific community and helps NCI monitor TREC's progress and productivity.

Teaming up to Study Diet and Cancer Risk

Through meetings, training, and an emphasis on collaborative research, Dr. Nebeling noted, TREC "creates a greater opportunity for investigators from different fields to start learning each other's vocabulary, find common ground, and work together in team science."

At the Hutchinson Center, one of the first four TREC research centers, members of one transdisciplinary team examined the effects of certain dietary patterns in cells, an animal model, and human subjects.

Drs. Johanna Lampe and Marian Neuhouser of the Hutchinson Center led a clinical trial of the effects of low and high glycemic-load diets on possible cancer risk biomarkers in people with normal body weight and body mass index (BMI) and in people who were overweight or obese, with high BMI. Low glycemic-load diets (those rich in foods such as legumes and whole grains) lead to a gradual increase in blood glucose after a meal, whereas high glycemic-load diets (which include foods such as white bread, white rice, and potatoes), which may be associated with obesity, cause a rapid rise in blood glucose and excess insulin secretion.

Some observational and epidemiologic studies have suggested that low glycemic-load diets are associated with a lower risk of certain cancers, "but very few controlled studies have been done to see if tweaking diet changes markers associated with risk," Dr. Lampe said.

Dietitians at Hutchinson designed the diets used in the study so that participants would not lose weight, allowing the researchers to "focus on whether any effects we observed were specifically diet related, rather than due to body weight change," Dr. Lampe explained.

For a related animal study, Dr. Lampe said, "we prepared all the meals that we fed to humans, ground them up and froze them down into little rat-size portions." She and Dr. Neuhouser sent the frozen rat rations to Dr. Henry Thompson, their collaborator at Colorado State University, who fed the diets to a strain of rats that spontaneously develop mammary tumors. Dr. Thompson compared the effects of the two diets on tumor development, which was not feasible in the human study because the duration was too short and it included a relatively small number of people.

Another Hutchinson Center TREC researcher, Dr. David Hockenbery, studied the effects of high glucose levels at the cellular level, looking at signaling pathways and other cell responses that may play a role in cancer development.

Results of the human and rat studies have not yet been published, but the benefits of a transdisciplinary approach seem clear. Being part of the TREC initiative, Dr. Lampe said, "had me thinking more broadly about our own experimental approach for addressing these questions [about diet, obesity, and cancer]. I also learned a lot from my colleagues in other disciplines."

Taking It to the Streets

Taking a transdisciplinary approach to understanding and preventing cancer linked with obesity was "a no-brainer" for Dr. Leslie Lytle, a nutritionist and behavioral scientist at the University of Minnesota, site of another of the first group of TREC centers. "In a school of public health, [where] we look at how we can change and improve the health behavior of populations," she explained, "you immediately realize that one person can't be an expert on everything you have to know."

Dr. Lytle led a TREC center project dubbed IDEA, for Identifying Determinants of Eating and Activity, to identify obesity-related risk factors in adolescents at the individual, family, school, and community levels. "We can speculate on what's causing the obesity epidemic in kids and adults, but we have very little data that actually [explain] how risk factors at different levels may be related to each other and to obesity risk in populations," she noted.

To guide her research, Dr. Lytle developed a conceptual model of potential risk factors with input from scientists from fields ranging from physiology to urban planning. With the model in hand, Dr. Lytle's team began following 349 young people in the Minneapolis-St. Paul area along with one parent or guardian for each youth.

One of the chief technologies the team used to investigate risk factors at the community level was a geographical information system (GIS) to assess the physical environment of neighborhoods. With GIS, Dr. Lytle said, researchers can link a child's address with publicly available databases to get information on the walkability of a neighborhood, the types of food stores and recreation facilities within a certain radius of the child's home, proximity to public transportation, and a host of other factors.

We need behavioral interventions that help prevent cancer in the first place.

—Dr. Lytle

Dr. Lytle and her colleagues used GIS to show a relationship between the built environment (buildings, spaces, and products created by people) and metabolic syndrome (which is linked to obesity) in adolescents; to examine how neighborhood food environments might affect adolescent nutrition, dietary intake, and weight; and to identify factors that predict levels of physical activity among boys and girls.

Numerous studies have examined the possible connections between neighborhood environments and health characteristics, Dr. Lytle said. But "in the IDEA study we are able to drill down much closer to the individual level" to nail down elements of the larger environment that are related to indicators of obesity.

Results of the IDEA study and others like it will have implications for public policies aimed at curtailing the obesity epidemic, such as urban planning. For instance, Dr. Lytle said, the findings "provide information about how we design a neighborhood to be more walkable, the need for more full-service grocery stores in urban areas, and the importance of creating parks and recreation areas that are accessible, well-lit, and friendly."

As researchers learn more about the root causes of cancers linked to obesity, Dr. Lytle said, "I feel strongly that we need behavioral interventions that help prevent cancer in the first place," not just better drugs to treat cancer once it occurs.

Moving Obesity Research from Bench to Trench

In the new phase of TREC, "we have greater integration from basic science to population science" and beyond, said Dr. Nebeling. The new phase also includes studies with more connections to cancer patients and survivors.

The TREC center at the University of Pennsylvania, for example, "was designed to go all the way, not just from mouse to human trials, but from mouse to policy, or 'from bench to trench,'" said Dr. Kathryn Schmitz, the center's principal investigator.

Dr. Schmitz, an exercise physiologist, is leading the centerpiece project, the Women in Steady Exercise Research (WISER) Survivor trial. This randomized trial will follow 555 overweight breast cancer survivors to assess the effects of exercise, weight loss through caloric restriction, and the two combined, on biomarkers for recurrence, quality of life, and lymphedema—a chronic and often devastating adverse effect of breast cancer treatment.

The trial is a follow-up to previous work by Dr. Schmitz, which showed that weight training can reduce the likelihood of lymphedema flare-ups in breast cancer survivors.

A second project, led by cancer biologist Dr. Lewis Chodosh, will study the same interventions as in the WISER Survivor trial in a genetically engineered mouse model for breast cancer recurrence. "We can't study the women through recurrence because the study is for only 5 years," explained Dr. Schmitz. But the mouse study will show whether exercise and/or caloric restriction can affect recurrence in overweight animals.

The mouse study will also measure a range of possible biomarkers of recurrence in the mice to gain insights into molecular pathways that might mediate recurrence. Those results will in turn inform Dr. Schmitz's decisions on which biomarkers to focus on in the WISER Survivor participants.

The third TREC project at Penn, led by internal medicine professor Dr. J. Sanford Schwartz, is a cost-effectiveness analysis of the WISER Survivor trial. The results "will help determine whether a low-cost intervention for lymphedema, namely exercise, could save money in the long run," said Dr. Schmitz. If so, she said, "we could change health care policy to approve payment for rehabilitation exercise programs for breast cancer survivors."

Dr. Schmitz is an enthusiastic advocate of transdisciplinary research. She emphasized the need for more communication between scientists across diverse disciplines and within related fields. "It's so much more productive—and fun—when you can look at things from different vantage points," she said, adding, "My favorite quote is from Albert Einstein: 'Play is the highest form of research.'"

Elia Ben-Ari

Related reading: "TREC Cancer Initiative Launches New Collaborative Relationships"

Special Issue: Cancer and Obesity Research

The Right Balance: Helping Cancer Survivors Achieve a Healthy Weight

The number of long-term cancer survivors in the United States is rising, as is the number of people who are overweight or obese, raising the specter that excess pounds could diminish length and quality of life for many who have survived cancer.

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Video produced and edited by Sarah Curry and Natalie Giannosa

Obesity has been linked with increased risks of recurrence and death in several cancers, including common cancers such as breast, colorectal, and prostate. For example, recent findings from the California Teachers Study, which enrolled 4,000 breast cancer survivors, showed that being obese at the time of study entry was associated with a substantial increase in the risk of dying from breast cancer in several subgroups, including women who had been treated for estrogen receptor-positive breast cancer.

The data supporting obesity's potentially deleterious impact on some cancer survivors is strong enough that clinical trials have been launched to help survivors control their weight.

The goal is not only to reduce the risk of cancer recurrence and death, according to Dr. Catherine Alfano of NCI's Office of Cancer Survivorship. "We know that cancer survivors face a multitude of chronic and late effects of cancer treatment that limit their ability to participate fully in their life roles and decrease their quality of life," Dr. Alfano said. Interventions that help survivors maintain a healthy weight, she continued, may also decrease the risk of obesity-related health problems like diabetes and heart disease.

Targeting At-Risk Survivor Populations

Woman on treadmill and interventionist NCI-funded researchers are testing diet and physical activity interventions in overweight and obese African American breast cancer survivors in an effort to reduce recurrences and improve quality of life.

Studies have shown that some cancer survivors are more likely than others to be overweight or obese. One such group is survivors of pediatric acute lymphoblastic leukemia (ALL). In a large study that involved participants in the NCI-supported Childhood Cancer Survivor Study (CCSS), adult survivors of pediatric ALL were substantially more likely than their siblings to be obese. Girls diagnosed with ALL before the age of 4 were nearly four times more likely than their siblings to become obese.

Steroids used to treat ALL can produce substantial weight gain. But other factors also affect weight gain and health over the longer term, noted Dr. Kevin Oeffinger of Memorial Sloan-Kettering Cancer Center in New York, the study's lead investigator. Obesity rates in ALL survivors in the CCSS study, he explained, were significantly higher in those who had been treated with high-dose radiation to the brain.

The radiation treatments "affect so many pathways that affect patients' muscle strength and development," Dr. Oeffinger said. Although roughly 80 percent of children diagnosed with ALL are cured, these types of long-term effects of treatment can greatly limit survivors' ability to be active, he said.

Primary Care-Based Programs Help Obese Patients Lose Weight

Obese patients lost an average of 10 to 11 pounds over 2 years with support and counseling programs managed by their primary care physicians, according to the results of two NIH-funded clinical trials published online this week in the New England Journal of Medicine.

Both trials were part of the Practice-Based Opportunity for Promotion of Weight Reduction Trials consortium funded by the National Heart, Lung, and Blood Institute. Consortium members are conducting clinical trials focused on helping obese people lose weight using interventions delivered in a primary care setting.

In each trial—one conducted at practices affiliated with the Johns Hopkins University and the other at practices affiliated with the University of Pennsylvania—approximately 400 obese patients with at least one additional cardiovascular risk factor were randomly assigned to weight-loss interventions that offered different levels of support or usual care. In both trials, participants who received counseling support (delivered in-person, over the phone, or both) over 24 months had substantially greater weight loss and were more likely to lose at least 5 percent of their initial body weight than patients who received minimal support or usual care.

Treatments for ALL can also have long-lasting cardiac effects, such as cardiomyopathy (a disease of the heart muscle), "and we know that obesity increases cardiovascular disease risk," Dr. Oeffinger continued. Future research is needed to more closely examine whether, and the extent to which, obesity can aggravate this underlying treatment-related cardiovascular risk, he said.

Obesity rates are also particularly elevated in endometrial cancer survivors, and as researchers have feared, those excess pounds are indeed detrimental to health. In one small study of overweight and obese endometrial cancer survivors, 43 percent had hypertension, 33 percent had metabolic syndrome, and 21 percent had type 2 diabetes. Fewer than half of participants reported engaging in even moderate exercise.

Trials Aim to Take Off the Weight

A number of trials to help overweight and obese cancer survivors shed weight are now under way. Most of the trials are in survivors of breast cancer and leukemia, but a small NCI-supported trial is also enrolling endometrial cancer survivors.

Researchers at the University of California, San Diego, Moores Cancer Center are enrolling overweight and obese survivors of childhood ALL in a small NCI-funded clinical trial. The trial aims to reduce participants' body mass index, explained the trial's co-principal investigator, Dr. Jeannie Huang. The weight loss intervention, which relies heavily on Internet and text messaging tools, is tailored to the needs of young cancer survivors, whose families are also involved in the process.

There is clearly a need for greater awareness of weight problems in ALL survivors and for effective interventions, Dr. Huang believes. "We're talking about a child or teenager who had a life-threatening illness, and you go from getting through that terror to what are perceived as more 'minor' health concerns, like putting on weight," she said. "The families are often simply happy that their son or daughter is alive and thriving, and don't recognize that weight gain puts them at risk for other health problems, as well as a secondary cancer."

One participant in the Moores trial, Ana Otanez, and her family are well aware of the need to maintain a healthy weight. Ana, who was diagnosed with ALL 10 years ago at the age of 6, said she has been seeing a nutritionist for "as long as I can remember." She learned about the trial during a visit with her physician, and she and her family agreed that it was worth pursuing.

Every morning, she receives text messages on her phone with guidance on physical activity and losing weight. "Things like 'don't eat seconds' and 'avoid junk food,'" she said. She also gets recipes for healthy meals via the trial's participant website. The recipes often end up as part of family meals.

"It really is a family thing," Otanez said. "My family really helps me and supports me." Her goal, she continued, is to lose at least 10 pounds during the trial's 4-month intervention period.

Targeted Interventions

A similar NCI-funded trial being conducted at Georgetown Lombardi Comprehensive Cancer Center is enrolling overweight and obese African American breast cancer survivors. (Learn more about the trial in the accompanying video.) African American women with breast cancer are more likely to die from the disease than their white counterparts and are also more likely to have more aggressive types of breast cancer.

"They're also more likely to be obese and have more comorbid conditions than Caucasian women," said Dr. Vanessa Sheppard, who, along with Dr. Lucile Adams-Campbell, is leading the trial.

Over a 3-month period, women in the trial receive nutrition counseling, have scheduled visits with trainers, participate in support groups, and receive weekly phone calls from a coach—a fellow breast cancer survivor—to check on their progress and to provide motivation and guidance. Like the ALL survivor trial, the Georgetown trial aims to lower BMI, change dietary and physical activity behaviors, and improve quality of life.

Help with weight management is clearly an unmet need for these women, Dr. Sheppard stressed. Before enrolling, only one of the women in the trial "had been referred to any type of nutritionist or had a referral for exercise by their oncologist," she continued. "So they can really benefit from this type of intervention."

Carmen Phillips

Applying Greater Energy toward Weight Loss

Researchers from the University of California, San Diego are leading the largest trial to date of weight loss in cancer survivors. Dubbed the ENERGY trial and funded by a $5.4 million grant from NCI, the 4-year, multisite trial will eventually enroll 800 overweight or obese breast cancer survivors.

Unlike some of the smaller trials in similar populations, the ENERGY trial's intervention component lasts 2 years. Participants are randomly assigned to an intensive-care arm or a usual-care arm.

The trial takes an aggressive, long-term approach toward weight loss in the intervention arm, including getting participants to build up to at least 1 hour a day of moderate to vigorous exercise. Participants attend weekly group counseling sessions for the first 4 months after enrollment. The group sessions are an important part of cognitive behavioral therapy, said the trial's lead investigator, Dr. Cheryl Rock. Many women have tried and failed to lose weight, Dr. Rock explained, so the therapy helps teach participants about the many aspects of behavioral and thinking patterns that are necessary to shed weight and keep it off.

"Social support is really important for people trying to lose weight, and also for cancer survivors," she continued. "Survivors have a lot of commonalties around what they have gone through, including fears that linger about recurrences, so that support is important."

Participants in the usual-care arm will receive individual counseling, educational support, and guidance on weight loss.

The trial's initial goal is to help participants achieve and maintain weight loss and improve their quality of life. But the hope, Dr. Rock stressed, is to eventually expand the trial to enroll approximately 2,500 women and follow them long enough to measure whether the intervention has an impact on breast cancer recurrence. "But even if we only show that survivors' quality of life is improved, that will be very important," Dr. Rock said.

Special Issue: Cancer and Obesity Research

NCI Information and Resources

NCI Research

National Institutes of Health Initiatives

  • WeCan! (Ways to Enhance Children’s Activity and Nutrition) – A program that provides tools, fun activities, and information to encourage healthy eating and more physical activity among children 8 to 13 years of age
  • NIH Obesity Research – Research areas, funding opportunities, and strategic plan for obesity research
  • The Genes, Environment, and Health Initiative – Research into genetic and environmental factors that may play a role in many conditions, including obesity
  • National Heart Lung and Blood Institute
    • Obesity Research – Information on NHLBI-funded obesity research
    • Aim for a Healthy Weight – A program designed to help people control their weight with tips and tools for healthy eating and exercise
  • National Institute of Diabetes and Digestive and Kidney Diseases
    • Obesity research – Resources for researchers and information on funding, research areas, and clinical research
    • Weight-control Information Network – Publications for consumers, health care providers, and community groups; statistics; and other resources

Department of Health and Human Services and Other Federal Initiatives

 

Cancer Research Highlights

Protein May Regulate Hormone Sensitivity in Breast Cancer

New research indicates that a protein called TWIST plays a key role in the aggressiveness and progression of breast cancers by regulating estrogen receptor (ER) expression. This discovery may ultimately open the door to new treatments for ER-negative breast cancers, which are more aggressive and harder to treat than ER-positive breast cancers, said the researchers who led the study. The findings, from investigators at the Johns Hopkins University School of Medicine and the University Medical Center Utrecht in the Netherlands, were published online November 7 in Oncogene.

Unlike ER-positive breast cancers, which rely on estrogen to grow and can often be successfully treated with drugs that block the action of this hormone, ER-negative breast cancers do not need estrogen to grow. According to the new research, the loss of the ER in TWIST-expressing cells causes the cells to grow independently of estrogen and to resist the effects of antiestrogen therapy.

Previous research had shown that the TWIST gene is overexpressed in some high-grade breast cancers and may play a role in breast cancer development. To investigate how TWIST may function, the researchers examined ER expression levels in breast cancer cell lines with varying levels of TWIST expression. This analysis showed that levels of TWIST protein were inversely related to levels of ER mRNA and protein. The investigators then demonstrated that TWIST represses the ER gene by preventing its transcription.

Subsequent experiments showed that breast cancer cells that express high levels of TWIST were able to grow in culture and to form tumors in mice in the absence of estrogen. These TWIST-expressing cells and tumors continued to grow even in the presence of the antiestrogens tamoxifen and fulvestrant. When the researchers used a technique to reduce TWIST levels in these cells, the cells produced substantially more ER and became sensitive to estrogen and antiestrogens.

To determine whether the inverse relationship between TWIST and ER that was seen in cell lines also holds true in human breast tumors, the investigators assessed TWIST and ER expression levels in 73 primary tumors. They found a statistically significant inverse correlation between TWIST and ER mRNA levels in grade 1 and 2 (but not grade 3) tumors.

“Now that we know that TWIST plays a major role in controlling estrogen resistance in breast cancer, we can investigate the value of antiTWIST therapies,” said senior author Dr. Venu Raman in a press release. For example, the authors suggest, such therapies might be able to render ER-negative cancers ER-positive, making them dependent on estrogen for growth and responsive to antiestrogen therapies.

Epigenetic Therapy Shows Potential in Advanced Lung Cancer

Treatment with drugs that target epigenetic changes in genes—chemical modifications that influence gene expression but do not involve changes in the sequence of DNA—showed promise in a small clinical trial of patients with advanced non-small cell lung cancer (NSCLC), researchers reported last week. The phase I/II trial is believed to be the first to demonstrate successful treatment of a solid tumor with epigenetic therapy. Findings from the trial, led by researchers from the Johns Hopkins University, were published November 9 in Cancer Discovery.

In the trial, 45 patients with metastatic NSCLC whose tumors had returned after previous treatment received low doses of azacitidine (Vidaza) and entinostat, two drugs that target epigenetic changes involved in silencing gene activity. Median survival among trial participants was 6.4 months, which is similar to what was seen in the clinical trials that led the Food and Drug Administration (FDA) to approve the targeted therapy erlotinib (Tarceva) for patients with advanced NSCLC. (The FDA approved azacitidine for the treatment of myelodysplastic syndromes in 2004.)

Among the patients who completed at least one cycle of treatment with the two drugs, median survival was 8.6 months. Seven patients from the trial are still alive, including two who began treatment approximately 4 years ago. The trial, which was sponsored in part by NCI’s Cancer Therapy Evaluation Program, did not include a comparison group of patients who did not receive the investigational therapy.

The treatment approach takes advantage of the fact that, unlike genetic mutations, epigenetic changes are potentially reversible. High doses of the drugs used in earlier trials were too toxic for patients, so the researchers used low concentrations that were sufficient to reverse epigenetic changes but that had limited toxic side effects, explained the study’s senior author, Dr. Charles Rudin, during a press briefing.

The two drugs “were well tolerated,” Dr. Rudin said, and the researchers were surprised to see tumor responses in two patients, including one complete response that lasted 14 months. Another 10 patients had stable disease. But he cautioned that the results need to be confirmed in a larger study population.

Patients whose tumors responded to the therapy improved gradually over several months of treatment, which suggested that the treatment was indeed working via an epigenetic mechanism, study co-author Dr. Malcolm Brock noted. After stopping treatment with the two drugs, 19 patients went on to receive at least one round of chemotherapy, other targeted therapies, or both. In four of these patients, including the two longer-term survivors, tumors shrank substantially after the additional therapy.

The findings should encourage continued research on epigenetic cancer treatments, including tests of epigenetic drugs in combination with standard therapies and identification of subsets of patients most likely to respond, Dr. Jeffrey Engelman of Harvard Medical School said during the briefing. Dr. Engelman was not involved in the study.

A small, multi-institution trial has been launched to test the same drug combination as a post-surgical, or adjuvant, treatment in patients with stage I lung cancer, Dr. Brock said.

Treatment Uses Antibodies and Light to Target Cancer Cells

Researchers from NCI’s Center for Cancer Research (CCR) led by Dr. Hisataka Kobayashi have developed a new type of targeted anticancer treatment using photoimmunotherapy—a light-activated “nano-bomb” bound to a monoclonal antibody (mAb) that delivers the cellular disruptor to tumor cells. In experiments in cells grown in the laboratory and in mouse models, the treatment effectively killed cancer cells that had an excess of a protein targeted by the mAb on their surfaces but spared normal cells. These results were published online in Nature Medicine on November 6.

Traditional photodynamic (light-activated) anticancer therapy uses compounds called photosensitizers that, when exposed to a specific wavelength of light, become activated and trigger cell death. However, in addition to killing cancer cells, photosensitizers can also damage normal tissue. To make the therapy more selective for cancer cells, Dr. Kobayashi and his colleagues created hybrid compounds (conjugates) that consist of a photosensitizer called IR700 bound to one of two mAbs, trastuzumab or panitumumab. These mAbs bind to cell surface proteins called HER2 and HER1, respectively, both of which are overexpressed by some cancer cells.

Cancer cells incubated in a laboratory dish with the conjugates for as little as 1 hour died when exposed to the near-infrared wavelength of light that activates IR700. This rapid action shows that the conjugates only have to bind to the cell surface to kill cancer cells—they do not need to be absorbed by the cell like traditional photodynamic therapy drugs. The conjugates did not kill cells that did not overexpress either HER2 or HER1.

To test the conjugates in an animal model, the researchers established xenograft tumors that overexpressed HER2 or HER1 in mice. After small tumors had formed, the researchers injected the mice with one of the two conjugates and exposed them to near-infrared light 1 day later. Mice that received the treatment had their tumors shrink significantly and lived longer than untreated control mice. The researchers did not observe any toxic effects in normal tissue after 4 weeks of twice-weekly administration of the conjugates.

The fluorescence from the new conjugates may also be useful in noninvasively diagnosing tumors and monitoring response to treatment, explained the authors. “Although more testing will be needed,” said Dr. Kobayashi in a press release, “we believe this [photoimmunotherapy] method has the potential to replace some surgical, radiation, and chemotherapy treatments.”

Genetic Mutation that Raises Melanoma Risk Identified

An international group of researchers recently identified a rare genetic mutation associated with an increased risk of melanoma. The mutation, a change in the MITF gene that alters one amino acid in the MITF protein, raises melanoma risk in people with a strong family history of melanoma and also in the general population, the researchers found. The study was published online November 13 in Nature.

Mutations in two genes, CDKN2A and CDK4, are known to increase the risk of familial melanoma, with CDKN2A mutations accounting for nearly 40 percent of familial melanoma cases and CDK4 linked to melanoma risk in a small group of families in which melanoma is common.

In an effort to identify additional genes associated with familial melanoma, lead investigators Dr. Kevin Brown of NCI’s Division of Cancer Epidemiology and Genetics, Dr. Nicholas Hayward of the Queensland Institute of Medical Research, and Dr. Jeffrey Trent of the Translational Genomics Research Institute sequenced the whole genome of several individuals with melanoma from families with multiple cases of the disease. None of the family members had an alteration in the CDKN2A or CDK4 genes.

In one individual, they found a variant in MITF. This gene is involved in numerous important functions in skin cells called melanocytes, the cell type from which melanomas arise. Previous studies have shown that MITF is amplified or mutated in some melanoma tumor samples and overexpressed in others, but none of the studies implicated the gene in risk of developing the disease.

Additional studies of the same individual’s family found the MITF gene variant, called E318K, in several family members who had developed melanoma, though not all. The authors then looked for the MITF variant in samples from two large case-control studies of melanoma involving the general population, as opposed to melanoma-prone families, and found that the E318K variant was carried more frequently by melanoma case subjects than by control subjects. The gene variant was found more often in families with a stronger history of melanoma, multiple primary melanomas, or both, Dr. Brown and his colleagues reported.

The mechanism by which the MITF variant may promote melanoma development is not yet clear, explained Dr. Brown, the study’s senior author. In studies involving cell lines, however, the researchers showed that the variant altered the expression of some of the genes known to be regulated by MITF.

The findings do not change recommendations for regular screenings and other protective behaviors in individuals with a family history of melanoma, Dr. Brown added.

FDA Update

Cetuximab Approved for Patients with Advanced Head and Neck Cancer

The Food and Drug Administration (FDA) last week approved the targeted drug cetuximab (Erbitux), in combination with chemotherapy, for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck.

The approval was based on the results of an international phase III clinical trial of 442 patients with metastatic or recurrent squamous cell cancer of the head and neck who had not previously received chemotherapy. Patients treated with cetuximab and chemotherapy (5-FU in combination with either cisplatin or carboplatin) had improved overall survival compared with patients who received chemotherapy alone (10.1 months versus 7.4 months). Patients who received cetuximab had a higher incidence of several side effects, including diarrhea, respiratory and other infections, and serious infusion reactions.

Cetuximab, which targets the epidermal growth factor receptor, is already approved for patients with nonmetastatic head and neck cancer and for some patients with advanced colorectal cancer.

Also in the News: Federal Judge Blocks FDA Graphic Cigarette Warning Labels

On November 7, U.S. District Court Judge Richard J. Leon, in response to a lawsuit brought by five tobacco companies, issued a preliminary injunction staying the Food and Drug Administration (FDA) from implementing and enforcing its rule requiring larger, more prominent graphic health warnings on cigarette packaging and advertising until 15 months after a final ruling by the district court on the merits of the legal challenge to the rule. 

The FDA published a final rule in June 2011, requiring that, as of September 2012, cigarette packages and advertisements contain graphic health warnings that cover the top half of the front and back of packages, and 20 percent of the area of advertisements. The new warnings contain nine different warning statements, each accompanied by a different graphic image. A requirement of the 2009 Family Smoking Prevention and Tobacco Control Act, the new health warnings mark the first change in cigarette warnings in more than 25 years. They are aimed at effectively communicating to consumers the specific health risks caused by smoking, including death, addiction, lung cancer, stroke, and heart disease.

Notes

NCI Board of Scientific Advisors Convened Last Week

NCI's Board of Scientific Advisors (BSA) met November 7 on the NIH campus in Bethesda, MD. 

Following a report from NCI Director Dr. Harold Varmus, NCI Deputy Director Dr. Doug Lowy, and Deputy Director for Clinical and Translational Research Dr. James Doroshow, attendees received a status update from the caBIG Oversight ad hoc Subcommittee, an update on the Chernobyl Tissue Bank, several presentations from the Division of Cancer Treatment and Diagnosis, and an overview of the NCI Center for Global Health.

The full agenda and a videocast of the public portions of the meeting are now available.

Free Webinar Will Address Vitamin D and Cancer Prevention

NCI's Frontiers in Nutrition and Cancer Prevention Series will continue December 2 with a free webinar on "Vitamin D and Cancer Prevention: Shining Light on the Current Research," from 12:00 to 1:30 p.m. ET.

Emerging evidence suggests that higher vitamin D exposure may reduce the risk of certain cancers in some populations but increase the risk in others. Experts in the field will discuss current nutritional guidelines, strength of current research, and some potential mechanisms by which vitamin D may influence cancer risk. The invited speakers and the titles of their presentations are:

  • "Vitamin D Overview: What Do We Know? What Do We Need to Know?"
    Dr. Gabriela Riscuta, NCI Division of Cancer Prevention
  • "Dietary Guidelines: How Much Is Enough? How Much Is Too Much?"
    Dr. JoAnn Manson, Harvard Medical School
  • "Clinical Research: Does Vitamin D Inhibit Cancer? How Strong Is the Clinical Evidence?"
    Dr. Donald Trump, Roswell Park Cancer Institute
  • "Basic Science: Potential Mechanisms for Vitamin D-Mediated Effects on Cancer Risk"
    Dr. James Fleet, Purdue University

For more information and to register, visit the Frontiers in Nutrition and Cancer Prevention website.

State-of-the-Science Conference on Active Surveillance for Prostate Cancer Slated for December

State-of-the-Science Conference: Role of Active Surveillance in the Management of Men with Localized Prostate Cancer cover art

On December 5–7, NCI and the NIH Office of Medical Applications of Research (OMAR) will convene a state-of-the-science conference on active surveillance for men with localized prostate cancer. The conference will take place at Natcher Conference Center on the NIH campus and will address the following key questions:     

  • How have the patient population and the natural history of prostate cancer diagnosed in the United States changed in the last 30 years?
  • How are active surveillance and other observational strategies defined?
  • What factors affect the offer of, acceptance of, and adherence to active surveillance?
  • What short- and long-term health outcomes have patients with localized prostate cancer experienced with active surveillance versus immediate treatment with curative intent?
  • What aspects of active surveillance (or watchful waiting) in localized prostate cancer need further research?

Invited experts will present information pertinent to these questions, and OMAR will prepare a systematic literature review. Conference attendees will have the opportunity to ask questions and provide statements during open discussion periods. After weighing the scientific evidence, an unbiased, independent panel will prepare and present a consensus statement addressing the key conference questions.

The conference is free and open to the public, but advance registration is recommended. For more information and to register, visit the conference website.