Obesity: A growing risk factor for cancer

Issue 21, Summer/Fall 2013

hamburgers and beer

While most people think of cancer as a wasting disease in which patients become emaciated, recent studies make it emphatically clear that obesity is associated with both an increased risk for many types of cancer and a worse prognosis or outcome for patients with cancer.

Once thought to contribute mainly to cardiovascular disease and diabetes, overweight and obesity are now known to increase the risk for multiple malignancies, including cancer of the colon and rectum, postmenopausal breast cancer, esophageal adenocarcinoma, liver and gallbladder cancer, kidney cancer, uterine cancer, pancreatic cancer, advanced prostate cancer, and several forms of blood cancer; the list continues to grow.

In fact, in the U.S., 14 percent of all cancers in men and one-fifth of cancers in women are associated with obesity. These statistics are even more alarming in view of the increased prevalence of obesity in both the U.S. and the world. Moreover, the increased incidence of obesity in children means that more people will be exposed to this cancerpromoting condition for longer periods of their lives.

Not only does being overweight boost the risk of cancer, it also contributes to cancer progression and is associated with worse outcomes in cancer patients, such as shorter survival. Furthermore, obesity complicates the treatment of cancer by making it more difficult for physicians to determine the correct doses for chemotherapy.

Energy In, Energy Out

Many factors contribute to the development of obesity, including increased availability and intake of energy dense foods, decreased physical activity and exercise, hereditary, psychosocial and environmental factors, and hormonal disorders. Microbes (microbiome) in the colon may also be a determinant of obesity. In the end, however, obesity represents the excess accumulation of fat in adipose tissue, due to increased energy consumption and decreased energy utilization.

Under normal circumstances, our daily energy requirements are filled by our dietary intake. When energy intake exceeds our needs for energy utilization, adipose tissue provides a reservoir in which to store energy reserves in the form of fat. As adipose tissue expands, it releases a series of messenger molecules known as hormones and growth factors to control appetite and regulate the process of nutrient storage and utilization.

However, obesity also leads to lowgrade inflammation in adipose tissue, and some nutrients, such as saturated fats, may also lead to inflammation. This results in the release of local and circulating inflammatory factors, called cytokines and adipokines, that may further promote cancer in a variety of ways, including altering hormone balance and directly promoting tumor cell growth. For example, obesity may lead to a condition known as insulin resistance. Adipose tissue, muscle, and liver require insulin in order to take up and utilize glucose for fuel. In insulin resistance, these tissues become resistant to insulin, forcing the pancreas to increase insulin production in order to support the ability of tissues to take up and utilize fuels. Because insulin has growth promoting effects, elevated insulin levels that occur during insulin resistance stimulate growth and progression of several tumor types. Likewise, many other hormones, cytokines, and adipokines associated with obesity, such as insulin-like growth factor-1 and leptin promote tumor growth and progression.

Lifestyle Change

Woman on Scale

Obviously, the most effective way to prevent obesity from increasing cancer risk and/or stimulating cancer progression is to lead a healthy life style, including consuming a moderate diet with an emphasis on plant foods, getting plenty of exercise and avoiding the development of obesity. More details of these guidelines are available through the American Cancer Society.

For people who are obese, weight loss brought about by diet and exercise has been shown to favorably change the circulating factors that stimulate cancer progression. However, it has been difficult to demonstrate that dietary management reduces cancer risk. This is, in part, due to the difficulty in conducting such a controlled trial, as well as problems in sustaining normal weight by dietary control. Despite this, several large series have shown that obese patients who undergo bariatric surgery (to alter the length and/or arrangement of the stomach and intestine to reduce absorption of dietary nutrients) have a reduced incidence of cancer as compared to obese patients not treated with bariatric surgery.

Similar lifestyle guidelines to those noted above are recommended for cancer patients undergoing or following cancer therapy, including consuming diets rich in plant foods with lowglycemic loads and reduced dietary fats and exercising on a regular basis. Studies of these lifestyle changes in cancer survivors have not yet shown extended time to tumor recurrence or improved survival. They have, nevertheless, shown a correction of some of the abnormal circulating obesity-associated adipokines, cytokines and hormones that promote cancer as well as showing an improvement in quality of life.

An interesting outcome of research investigating the relation of obesity to cancer is the observation that agents -- such as metformin -- used in the treatment of insulin resistance and diabetes and useful for controlling some of the metabolic consequences of obesity are now being tested as cancer prevention and therapeutic agents.

The ongoing obesity epidemic continues to hamper efforts at preventing many diseases, including cancer. Only research -- into better ways to prevent and control excess weight gain, and to identify and disrupt the mediators that link obesity with cancer -- will help turn this situation around.

Nathan A. Berger, MD

Nathan A. Berger, MD
Distinguished University Professor
Professor of Medicine, Biochemistry, Oncology and Genetics
Director, Center for Science, Health and Society
Case Western Reserve University
Cleveland, OH