Obesity directly tied to several cancers

"Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible. Further, obese cancer patients do worse in surgery, with radiation or on chemotherapy - worse by any measure." Karen Basen-Engquist, Ph.D., Director of MD Anderson's new Center for Energy Balance in Cancer Prevention and Survivorship and professor of Behavioral Science.

These concerning facts from The University of Texas MD Anderson Cancer Center point to one of the most critical health issues facing Americans today. While the links among obesity, diabetes and heart disease are well-known, there is considerably less public awareness that obesity is also directly tied to several cancers. These include some of the toughest to treat: postmenopausal breast; cervical; ovarian; colon and rectal; endometrial, esophageal; thyroid; gallbladder; kidney; and pancreatic cancer. Studies also show higher recurrence and mortality rates for overweight and obese patients and survivors.

The battle against obesity is difficult, as unhealthy behaviors are established early in life and challenging to break. While smoking has declined in the last 40 years, adult obesity more than doubled between 1970 and 2010. The past three decades have seen childhood obesity rates triple in the U.S. By 2030, these trends could add an estimated $66 billion in annual obesity-related medical costs, over and above today's $147 billion to $210 billion.

MD Anderson is leading efforts to better understand the mechanisms behind the obesity-cancer connection, how obesity impacts cancer treatment outcomes and novel methods of prevention to curb cancer risk. Following a multidisciplinary approach, with various specialties and departments coming together to piece together this complex puzzle, researchers focus on obesity across the entire cancer continuum, from prevention to survivorship.

Most recently, MD Anderson established the Center for Energy Balance in Cancer Prevention and Survivorship, one of the few comprehensive research-focused initiatives dedicated to basic and clinical research.

Behind the Obesity-Cancer Link: Possible Biological Mechanisms
In 2007, more than 50,000 new cases of cancer in women (7 percent) and 34,000 new cases in men (4 percent) were due to obesity. The percentage of cases attributed to obesity varied by cancer type but was as high as 40 percent for some cancers, particularly endometrial cancer and esophageal adenocarcinoma.

While researchers have yet to pinpoint exactly how obesity increases cancer risk, a number of biological mechanisms may be at work:
 Fat creates an environment where cancer-promoting factors ooze. For example, fat tissue produces excess amounts of estrogen, high levels of which have been associated with some cancers. Obesity may also increase levels of insulin and insulin-like growth factor-1, which causes insulin resistance and may promote cancer development.
 Fat cells also appear to "flip the switch," affecting tumor growth regulators - a key mechanism of cancer progression - and perhaps producing hormones that stimulate or inhibit cell growth.
 Finally, obesity is associated with chronic inflammation, also linked to cancer risk.

The Center for Energy Balance in Cancer Prevention and Survivorship
MD Anderson's Center for Energy Balance in Cancer Prevention and Survivorship was founded to bring the center's formidable research-based multidisciplinary approach to better understand the effect of obesity on cancer risk, outcomes and survivorship. Funded in part by the Duncan Family Institute for Cancer Prevention and Risk Assessment and housed within the Division of Cancer Prevention and Population Sciences, the center is led by Karen Basen-Engquist, Ph.D., professor of Behavioral Science. It is MD Anderson's response to national research agendas addressing the role of obesity, diet and exercise in cancer, and developing solutions to the country's obesity epidemic.

Building on MD Anderson's ongoing research in the field, it is working to facilitate collaboration among investigators - including partnerships with other institutions - and expand infrastructure for basic and clinical research in three broad areas:
 The effect of exercise, nutrition and weight control on outcomes in cancer survivors and people who have an increased risk of developing cancer;
 Dissemination and implementation research related to energy balance interventions; and
 Behavioral science research in exercise, eating behavior and weight loss.

MD Anderson researchers anticipate that the center's work will lead to evidence-based changes in the clinical practice standards throughout cancer institutions and advance policy initiatives aimed at reducing obesity-related cancer risk.

"Among the many important and potentially profound efforts that the center is undertaking is informing local, state and national initiatives to tackle the alarming obesity rates," said Basen-Engquist. "These rates will continue to grow, adding to the oncoming wave of individuals with chronic diseases, including cancer, unless they're addressed - and reversed - systematically."

Basen-Engquist is currently working on a National Cancer Institute (NCI)-funded study investigating the mechanisms of exercise adoption and maintenance in endometrial cancer survivors. The study is testing the social, psychological and behavioral predictors of a person's ability to initiate and continue an exercise program. Findings of this and other studies will become a hallmark of the center's commitment to offer the most up-to-date care informed by energy balance and survivorship research.

Addressing Obesity from the Bench to the Bedside

Understanding the role of weight in cancer treatment and outcomes is crucial, as evidence suggests that obesity affects prognosis, the development of secondary cancers and survival. Excess weight can make it difficult to detect tumors, as obese patients may not fit into machines, such as CAT scans. Proper chemotherapy dosing in obese patients is also an area of clinical debate because the standard approach of calculating dose based on total body surface fails to take into account the body's composition, such as fat percentage, and may lead to suboptimum doses.

A range of basic and clinical trials designed to address issues pertinent to patients' treatment and survivorship are underway at MD Anderson. Ann Klopp, M.D., Ph.D, assistant professor in the Department of Radiation Oncology, is examining how fat impacts cancer outcomes. Her work, specifically on ovarian cancer, has shown that fat cells directly affect tumor growth because they contain stem cells, which can migrate into nearby tumors and support tumor cell growth. Klopp's findings will increase understanding of obesity's role as an ovarian cancer risk factor and could lead to drugs that block stem cells' effects on tumor growth and spread.

At the clinical level, MD Anderson led the testing of an experimental drug shown to starve fat cells by destroying their blood supply. In obese rhesus monkeys, the drug resulted in an 11 percent decrease in body weight over four weeks - lowering body mass index and reducing body fat.

Focusing on Obesity Prevention: From Lifestyle to Novel Preventive Agents
"We know obesity plays a significant, causal role in developing cancer, but it's hard to say how it contributes to a person's overall cancer risk," says Donghui Li, Ph.D., professor, Department of Gastrointestinal Medical Oncology. "Age, ethnicity, family history and numerous other risk factors are also at work. Our research aims to shed light on who will develop cancer and why."

In one of the first studies to explore at which ages excess weight predisposes an individual to pancreatic cancer, Li found that those who became obese between ages 14 and 19 had a 100 percent increased risk.

While obesity is associated with many types of cancer, it is most closely linked to endometrial cancer - the most common cancer of the female reproductive system and one that occurs primarily in obese women over age 40. In fact, obesity increases a woman's endometrial cancer risk two-fold. Karen Lu, M.D., professor in the Department of Gynecologic Oncology, has led pioneering research that found insulin resistance associated with obesity contributes to the increased risk of endometrial cancer.
Li and Lu are currently investigating potential medications to prevent obesity-related cancer. Their research is focused on the use of the most commonly prescribed anti-diabetic drug, metformin, which studies have proven may reduce a diabetic's risk of pancreatic cancer by more than 60 percent. Currently in clinical trials at MD Anderson and in collaboration with other institutions nationwide, this work underscores the importance of interdisciplinary collaboration, as diabetes and cancer have not traditionally been studied together.

In another related example, Drs. Lu and Basen-Engquist are also exploring how metformin and lifestyle interventions may work individually and in combination to lower biomarkers for, and thus, prevent endometrial cancer.

Nutrition & Exercise = Powerful Preventative Lifestyles
Prevention measures also include the tried-and-true approaches: eating healthier, exercising more. A number of MD Anderson programs aim to get patients, families and whole communities to adopt healthier lifestyles that can prevent cancer from the start.

Several of these efforts concentrate on children and young adults, as lifestyle behaviors are often formed at this stage and because more than one-third of childhood cancer survivors in the U.S. are obese or overweight - a statistic mirroring the general public. Cancer therapy can make eating difficult and unappealing, thus parents frequently allow children to eat anything they want, setting a pattern of unhealthy behaviors that persist after treatment ends. Pediatric patients' treatment also predisposes them to a higher risk of heart disease, diabetes and secondary cancers, so reducing these risks is critical.

The ON (Optimizing Nutrition) to Life Program, founded and directed by Joya Chandra, Ph.D., associate professor at MD Anderson Children's Cancer Hospital, promotes healthy eating habits in patients and survivors through education, behavior sciences and innovative research. The newest ON to Life initiative is @TheTable, a free, online, mobile-enhanced cookbook with healthy, kid-tested recipes geared toward patients and the healthy public. Dr. Chandra is also studying a video game-based intervention originally created for diabetes prevention to encourage healthy eating.

Susan Schembre, Ph.D., assistant professor, Behavioral Science, is focusing her research on adults and the neurological mechanisms behind food addiction - similar to drug addiction - in obese individuals. She is currently comparing brain reactions to food stimuli in obese and normal weight people to determine if altered reward circuits in the brain are related to obesity and the risk for weight regain after weight loss.

Exercise is also crucial for cancer prevention and may improve prognosis. A number of MD Anderson studies are currently exploring the effect of exercise on cancer outcomes, such as cardiac function and symptoms in survivors who experience heart failure after chemotherapy; fatigue in prostate cancer patients undergoing radiation; and overall physical functioning in breast cancer survivors.

Further, exercise reduces the risk of obesity-related chronic illnesses - such as hypertension, heart disease, stroke and diabetes - for which cancer survivors are predisposed, either because the diseases share risk factors with cancer or because cancer treatment leaves survivors more vulnerable to their effects.

iMove, the latest clinical trial of Lorna McNeill, Ph.D., M.P.H., associate professor in the Department of Health Disparities Research, is focused on understanding social and environmental influences on physical activity in sedentary minority adults, particularly targeting Latinos and African-Americans - populations that have the lowest rates of physical activity. Funded by the National Cancer Institute, iMove is a community-based lifestyle program that examines the influences - from cultural behaviors to depression - that affect a person's ability to initiate and maintain an exercise program, and identifies changes that occur during the course of physical activity, such as a reduction in perceived environmental barriers and psychosocial stressors.

Finally, through community-based efforts, MD Anderson experts are also focused on addressing health policy issues that impact the obesity-related cancer burden. "Ensuring that communities have safe places for outdoor exercise, such as sidewalks and bike lanes, and supporting better nutrition in schools are just a few of the ways we can reduce obesity rates," says Lewis Foxhall, M.D., MD Anderson's vice president for Health Policy.

Coming Together When Illnesses Cross
From the cellular level to the individual to communities and society, the links between obesity and cancer are not yet fully understood. But this is certain: unraveling the complex connections will require an approach that looks at the problem from different perspectives and knowledge bases, from behavioral modifications to novel drug development. Researchers must also explore obesity and cancer in relation to other related illnesses, such as chronic inflammation and diabetes.

MD Anderson is bringing together scientists and clinicians from across the institution and in collaboration with other specialists, community groups and patients to address obesity at every level of care. The findings may soon change the way obesity is understood as it relates to cancer, how obese cancer patients are cared for - during and after treatment - and, eventually contribute to helping stem the obesity crisis.