Frontline Cancer: Exploring the link between obesity and cancer

More than two-thirds of U.S. adults are overweight or obese, which comes with a long and heavy list of associated health risks, among them: coronary heart disease, stroke, high blood pressure, type 2 diabetes — and cancer.

An ever-growing number of studies show that packing on excess pounds increases the risk for cancer, most notably colon, pancreas, kidney, thyroid, breast, endometrial (uterine), esophageal and gallbladder.

The numbers are alarming and likely to worsen. In 2007, the National Cancer Institute (NCI) estimated that 34,000 new cases of cancer in men (4 percent of the annual total) were due to obesity. For women, it was 50,500 news cases or 7 percent of the total. If obesity trends continue, the NCI projects roughly 500,000 additional cases of obesity-caused cancer by 2030.

Cancer is already the nation’s second most common cause of death after heart disease, killing more than 585,000 Americans each year. A bulging obesity rate gives it a better shot at becoming the number one killer.

It’s difficult to say how exactly obesity fits into the cancer-causing equation. It’s a complex disease. Each cancer patient is different, with his or her own unique biology and environmental exposures. Nonetheless, several biological mechanisms have been proposed to explain the association.

Fat tissues produce excess amounts of estrogen

and high levels of this hormone have been linked to greater risk of breast, endometrial and other cancers.

Obese people often have increased levels of insulin

and insulin-like growth factor-1 in their blood, which may promote development of certain tumors.

Fat cells produce hormones called adipokines

that may abnormally stimulate cell growth. Cancer is fundamentally a disease of cell growth run amok. Fat cells may also directly or indirectly affect other regulators of tumor growth.

Obese people often suffer from chronic, low-level inflammation

, which is associated with increased cancer risk. Indeed, Michael Karin, Ph.D., distinguished professor of pharmacology and pathology at the UC San Diego School of Medicine and a faculty member at Moores Cancer Center, and others have shown that obesity-induced inflammation promotes development of liver cancer, the third leading cause of cancer-related deaths worldwide.

Other possible mechanisms

include altered immune responses and oxidative stress.

Does losing weight lower cancer risk?

The answer would seem to be yes, but again it’s hard to know with certainty. Research has demonstrated that weight loss reduces the risk of developing diabetes and improves risk factors for cardiovascular disease. Studies of patients who have undergone bariatric surgery to lose substantial amounts of weight show they have lower rates of obesity-related cancers than similar obese patients who have not had the surgery.

But unlike, say, tobacco consumption and lung cancer, there is no smoking gun that inextricably and indisputably links obesity to cancer. Not yet, at least. These efforts continue with scores of studies. For example, a team led by Ruth Patterson, Ph.D., director of the Transdisciplinary Research on Energetics and Cancer center at Moores, is conducting a randomized trial testing the impact of weight loss versus metformin (an anti-diabetic agent) on breast cancer recurrence using a design to link changes in metabolic health to breast cancer risk. The study is part of a larger program sponsored by the National Cancer Institute.

Eventually, I believe definitive answers will be found, or the steady accumulation of studies linking obesity and cancer will overwhelm any contradictory opinions.

In the meantime, researchers from

the San Diego Prevention Research Center at San Diego State University (SDSU) and from Moores Cancer Center are pursuing proactive remedies, such as operating free physical activity classes in different communities. At 34 percent, San Diego County has a high prevalence of obesity. Rates are even higher next door in Imperial County, particularly among children (47 percent overweight or obese compared to 38 percent for all of California).

These children are the focus of a Childhood Obesity Research Demonstration study, funded by the Centers for Disease Control and Prevention and headed by Guadalupe X. Ayala, Ph.D., MPH, a Moores Cancer Center member at SDSU. The study is testing whether a whole-child approach to preventing and controlling obesity can change the next generation’s life expectancy.

—Scott M. Lippman, M.D., is Director of UC San Diego Moores Cancer Center. His column on medical advances from the front lines of cancer research and care appears in the La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman at mcc-dir-lippman@ucsd.edu