University of Colorado Cancer Center Researchers Link Extra Fat Around the Waist to Increased Cancer Risk and Death

Americans overwhelmingly rank cancer as their No. 1 health concern, far outstripping concerns about obesity. But it turns out that rather than independent health concerns, the conditions are linked. Worried about cancer? Take care of your weight, say University of Colorado Cancer Center researchers.

According to the American Institute for Cancer Research (AICR), every year an estimated 110,000 cancer deaths in the U.S. can be attributed to obesity, making it the second leading cause of cancer deaths, behind smoking.

Besides raising the risk of dying from cancer, obesity also elevates the risk of developing cancer. Seven types of cancer are strongly associated with obesity: endometrial, esophageal, pancreatic, kidney, gallbladder, breast and colorectal.

One U.S. study, using National Cancer Institute Surveillance, Epidemiology, and End Results data, estimated that in 2007 nearly four percent of new cancer cases in men and seven percent in women were due to obesity. While cancer percentages due to obesity varied widely by cancer type, endometrial cancer and esophageal adenocarcinoma were the highest.

Colorado’s obesity rate may be the lowest in the country, but even here the rate is climbing and at an alarming rate. From 1995 to 2008, Colorado’s obesity rate climbed 89 percent, while the number of obese adults nationwide rose 67 percent, according to the Colorado Department of Public Health and Environment.

“Everyone in Colorado likes to brag that we’re the thinnest state,” says Ann Thor, MD, CU Cancer Center investigator. “But it’s cause for concern that the state’s rate is growing faster than the rest of the country. At this rate, we’re going to continue to see jumps in obesity’s comorbidities–heart disease, diabetes and cancer.”

A Balancing Act: Apples Versus Pears

All fat isn’t created equal.

Subcutaneous fat, which lies directly under the skin and is found on the upper arms, buttocks, hips and thighs, is the body’s protective wrap and energy store. Visceral fat found deeper in the body cushions the body’s vital organs and contributes to belly bulge. It’s this bulge that equals poorer health, says Thor.

“We’re starting to look more at a person’s body fat distribution,” Thor says, “and the central fat around a person’s abdomen, or an apple-shaped body, appears to be particularly troublesome.”

While eating an apple a day keeps the doctor away, looking like one predicts cancer risk. Conversely, pear people (who collect fat in their hips and thighs) have lower risk despite equal overall rates of fat. To be considered healthy, waist measurements should be under 40 inches for males and under 35 inches for females. Anything above that equals higher cancer risk.

“Really it comes down to does a person store their extra fat above the waist or below the waist,” says Paul MacLean, PhD, CU Cancer Center investigator.

Researchers also take into account body mass index (BMI) or a person’s weight-to-height ratio when understanding obesity. A BMI of 18.5 to 24.9 is generally regarded as healthy or normal. At more than 25, a person is considered overweight; more than 30, they’re obese. However, BMI doesn’t take into account a person’s waist measurement. A person can be labeled obese according to BMI, but healthy according to waist measurement.

“Essentially, it’s all about where the fat is gained and when the fat is gained,” Thor says.

Fat’s Attack on Age

If you thought fat’s greatest assault was on how others perceive your bikini body, think again. It may be on the inside and not on the outside that fat does the most damage.

Scientists have found that fat cells around the waist boost the body’s production of hormones such as estrogen, insulin and insulin-like growth factor 1—all of which cause cells to divide more rapidly. Fat also produces a variety of proteins that cause chronic inflammation, supporting cell growth. Both are characteristics of cancer.

In women, lifetime exposure to estrogen can positively or negatively impact their risk of developing hormone-associated cancers: breast, ovarian and endometrial. Early menarche, late menopause and not bearing children all increase a woman’s exposure to estrogen, and correlate with increased cancer risk.

Coupled with post-menopausal weight gain, overweight or obese women have a higher incidence of breast cancer since cancer cells are fueled by glucose. The more glucose the body has, the more fuel cancer cells have to aid their growth and dispersal.

“Even if a woman is not overweight or obese prior to menopause, the average woman gains 20 pounds post-menopause; and it’s usually within the first few years,” says MacLean. “It’s this rapid weight gain that we’re concerned about.”

MacLean and other CU Cancer Center researchers believe if they can identify the peri-menopausal window, they can potentially reduce glucose levels, rapid weight gain and elevated estrogen levels in women.

“If we can find the window where everything comes together, it may be possible to develop prevention and treatment strategies that specifically target the risk window of menopause,” says Pepper Schedin, PhD, investigator and co-director of the Young Women’s Breast Cancer Translational Program at the CU Cancer Center.

Fat, Rats and A Big Window

In 2005, Schedin wanted to learn more about obesity and its potential impact on breast cancer. She was introduced to MacLean, an expert in obesity and nutrition. The two joined forces to apply for a CU Cancer Center seed grant to study whether obesity promoted post-menopausal breast cancer.

The grant allowed them to make fat rats. The team started off with two groups of rats: lean and obese. Both groups underwent surgical ovarectomy, were fed high-fat, “western diets” and had prior tumors. Regardless of whether the rats were lean or obese, both groups gained a lot of weight, says MacLean.

“The obese rats had more tumors that progressed and less that regressed.” MacLean says. “No matter how you look at it, the obese rats came out of ovarectomy with more tumor burden and incidence.”

But the research team wanted to take it to the next level. Schedin and MacLean recruited two more CU Cancer Center investigators: Steve Anderson, PhD, an expert in breast cancer molecular biology, metabolism and glucose utilization; and Thor, an expert in dietary factors and hormones. The four became the “Fat Rat Group.”

Looking back on data, the team was surprised by the short period of time it took the rats to gain the weight—all during the three weeks post ovarectomy. This spurred the team to consider interventions that could be utilized prior to high-risk women hitting menopause.

“In normal women the menopausal transition can vary from one to several years, or it can be very quick if a woman has a hysterectomy for other health-related reasons,” says Schedin. “That’s a big window to target. But, if we can find high-risk women, who may have a family history of breast cancer, prior to menopause, we may be able to alter their future health outcomes.”

Metformin: A Historical Wonder

In 2008, the ‘Fat Rat Group’ was awarded a three-year, $600,000 grant from the Susan G. Komen for the Cure Foundation to try a drug on their fat rats—a common diabetes drug called metformin, which Thor had found killed breast cancer cells.

Knowing that the body’s tissues “don’t clear glucose fast enough” in the obese condition, Anderson says that clearing glucose may be an opportunity to improve metabolic regulation in post-menopausal women. This is where the wonder drug metformin comes in.

“In our current study, we want to show that metformin stabilizes blood glucose levels, stops the breast cancer tumors from growing and improves overall metabolic function,” Anderson says.

While metformin has been around since the mid-1900s, it’s just begun to be studied in epithelial cancers—breast, lung, colon and prostate. Data suggests that metformin reduces breast cancer cells’ addiction to sugar, inhibits tumor growth, and induces cell death making this inexpensive, easy to come by and low-toxicity drug exciting, says Thor.

“Metformin has the possibility of preventing cancer,” Thor says. In the long run, Thor believes metformin will reduce the incidence of breast cancer in patients with diabetes, but she believes physical activity and diet should be part of the equation.

Dropping the Fat, Improving the Outcomes

The NCI estimates that one-third of cancers can be prevented through diet, physical activity and weight management. However, researchers haven’t discovered the magic number of pounds it takes to reduce cancer risk.

At the CU Cancer Center, cancer prevention and control experts Tim Byers, MD, MPH, and Rebecca Sedjo, PhD, are conducting an new trial called Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY)—an NCI-funded study looking at the effects of weight loss on quality of life and eventually cancer recurrence in breast cancer survivors. Four cancer centers are following 800 participants over the course of two years.

“Typically if breast cancer survivors are heavier they have worse outcomes for recurrence and mortality,” Sedjo says. “Right now, we think that weight loss can change those outcomes but there is no population data. This study will be the first to really help answer that question.”

While researchers can’t conduct clinical trials requiring people to gain weight, they can help people lose it. Preliminary studies suggest that even modest levels of weight loss among the obese may reduce cancer risk. The ENERGY trial is encouraging participants to lose seven percent of their body weight—a number that has shown to reduce the risk of diabetes and poor cardiovascular health.

But researchers know that weight loss isn’t easy. One way to encourage weight loss is to connect dieters with a support group of like-minded dieters, and so the ENERGY trial is designed to build an instant support group.

“The great thing about the ENERGY trial is all of the participants are breast cancer survivors, all of them are overweight, and all of them are women creating an ideal support system needed for weight loss,” Sedjo says.

Only time will tell if the ENERGY trial produces the results necessary to improve cancer outcomes. In the meantime, CU Cancer Center researchers like Thor, MacLean, Anderson, Schedin, Byers and Sedjo will continue building the connections between obesity and cancer, and convincing people that ‘pears’ are better than ‘apples.’

“Here at the CU Cancer Center, we’re really in an ideal position,” MacLean says. “We have cancer and metabolic researchers who are all interested in understanding the relationship between obesity and cancer, coming together under one roof.”

“And instead of waiting until people get cancer and then treating it, we’re figuring out ways to prevent it,” adds Thor