Fall 2012

By Justin Matlick

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Like many of us, Dr. Mario Kratz spends a lot of time obsessing over fat. But his attention isn’t focused on his waistline.

A nutrition researcher at Fred Hutchinson Cancer Research Center, Kratz studies how obesity increases the risk of cancer and other chronic health problems—and he is conducting some of the world’s most innovative studies on how improving a person’s eating habits might break that link. His work could ultimately redefine the guidelines that tell us what we should eat, and could help people know exactly which foods elevate their cancer risk.

“Obese people have a much higher risk of getting cancer and of dying from it,” Kratz said. “If we can understand why this is and how diet contributes to it, we can prevent many of these deaths.”

Dr. Mario Kratz
Dr. Mario Kratz
Kratz’s research exemplifies how the Hutchinson Center is at the forefront of understanding—and potentially defusing—what is becoming a major new cancer epidemic. Being overweight or inactive is known to increase a person’s risk of some of the most common cancers—including colorectal cancer, breast cancer and certain prostate cancers—and is also linked to cancers of the esophagus, pancreas, kidney, thyroid and gallbladder.

With more than two-thirds of Americans now obese or overweight, the National Cancer Institute projects obesity will lead to about 500,000 new cases of cancer in the United States by the year 2030.

The threat is so severe that the Hutchinson Center’s Dr. Anne McTiernan, whose groundbreaking research pinpoints how weight loss and exercise reduce cancer risk, likens obesity to another insidious problem that took decades to diminish.

“Obesity is almost like the new smoking,” McTiernan recently told the Los Angeles Times. “The effect isn’t as big for most cancers, but it’s so prevalent that it will have a huge impact.”

It’s a problem with global implications. Earlier this year, the respected medical journal The Lancet reported that sedentary lifestyles, often associated with obesity, kill 5.3 million people worldwide per year—slightly more than smoking.

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‘The epidemic of our time’

The first step in taking on an epidemic is to prove it exists. While this sounds obvious, it’s a key part of establishing the scientific foundation needed to build new treatments and prevention strategies.

When the medical community started noticing more cancer cases among obese people, Hutchinson Center researchers led some of the first studies confirming this ominous trend.

Dr. Alan Kristal, a Hutchinson Center epidemiologist, was the first to show that obesity is associated with an 80 percent increase in a man’s risk of

Dr. Alan Kristal
Dr. Alan Kristal
developing aggressive prostate cancer. Dr. Amanda Phipps, working with colleagues in the Hutchinson Center-based Women’s Health Initiative, discovered that women with high body-mass indices (an indicator of body fat) have up to a 35 percent higher risk of getting triple negative breast cancer.

Recently, the Hutchinson Center was selected by the National Cancer Institute to coordinate one of the largest and most comprehensive efforts to unravel the obesity-cancer connection, the Transdisciplinary Research on Energetics and Cancer (TREC) initiative.

“Obesity is the epidemic of our time, and we desperately need to turn the corner on it,” said Dr. Ross Prentice, director of the Hutchinson Center’s Public Health Sciences Division, which studies large populations of people to find ways to reduce the risk of cancer and other diseases. “Our prevention research is a crucial piece of this response.”

Diagnosis and death rates for cancer have fallen in recent years in the U.S., thanks to scientific innovations that have improved methods for detecting, treating and preventing cancer—the direct results of work by the Hutchinson Center and other research institutions.

But with no end in sight to the obesity epidemic, the rise in obesity-related cancers could reverse some of these gains. And that puts the onus on researchers to figure o

Dr. Amanda Phipps
Dr. Amanda Phipps
ut how obesity leads to cancer.

“We’re where we were with smoking in the 1960s,” said Dr. Mark Thornquist, a Hutchinson Center researcher who directs the TREC coordinating center. “We have plenty of evidence that obesity is bad for us, but no good strategies on how to defeat it."

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Unraveling how obesity triggers cancer

Not long ago, scientists believed fat cells didn’t really affect how the body functions. They thought fat was just a place to store excess energy, like an extra gas tank in a car. Then, in the 1990s, researchers made a surprising discovery: Fat cells secrete hormones.

“That totally changed our perception of fat tissue,” Kratz said. “If it secretes hormones, it’s more than just a storage tank—it might be more like a gland.”

Now Kratz is spearheading research into how fat sparks cancer and other chronic diseases. As he explains it, there are three big keys to the obesity-cancer equation.

Dr. Mario Kratz

The first one focuses on the hormones produced by fat. These include estrogen, which makes certain cancers grow faster, including common types of breast cancer. This is especially worrisome in obese women who have gone through menopause.

Because excess fat keeps their estrogen levels up at a time when they should decline, postmenopausal women face increased breast cancer risk. Obese men aren’t immune: The male sex hormone, testosterone, is converted to estrogen in fat tissue, reducing their fertility.

Insulin—which regulates how the body absorbs sugar—is a second key factor. Because obese people’s cells often are resistant to insulin, their bodies compensate by producing abnormally high amounts of it, triggering a condition called hyperinsulimia. Insulin is like estrogen—it promotes cancer growth.

“Obese people can have insulin levels that are several times higher than they should be,” Kratz said, “and that predisposes them to developing cancer and could also help the cancer grow faster.”

Kratz’s research zeroes in on a third factor—inflammation—that he thinks might be the linchpin to explaining how obesity increases the risk of cancer and other chronic health problems. His innovative work could be a game changer in understanding the obesity-cancer link.

In some obese people, but not in all of them, the fat tissue gets inflamed. But unlike normal inflammation, which spikes around an injury and recedes as the injury recovers, the fat tissue’s inflammation doesn’t go down. Rather, obese people’s bodies are in a state of constant, low-grade inflammation.

“If we can understand what contributes to this inflammation, I believe we can understand the link not only between obesity and cancer, but between obesity and diabetes, cardiovascular disease and other chronic health problems better,” Kratz said.

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Focus on preventing cancer before it starts

Kratz and his colleagues are trying to find practical ways to reduce the risk of obesity-related cancers. It’s a priority that reflects the Hutchinson Center’s commitment to prevention—and its status as the home to the world’s largest and most established research program dedicated to uncovering the factors that influence a person’s likelihood of getting cancer.

Dr. Anne McTiernan
Dr. Anne McTiernan
When Dr. Anne McTiernan came to the Hutchinson Center in the 1990s, her goal was to find ways to help women cut their breast cancer risk. Since then, her prolific, groundbreaking work has illuminated much of what we now understand about obesity and cancer risk. McTiernan’s research measures how exercise and weight loss affect the levels of estrogen, inflammation and other so-called “biomarkers” that are linked to cancer.

One of her earlier studies found that women who get regular, moderate exercise whittle away particularly dangerous belly fat and also lower their insulin, estrogen and testosterone levels—and reduce their risk of breast cancer, heart disease and diabetes in the process.

Another McTiernan trial found that men who regularly exercise six days a week lower their markers of risk for colon cancer.

McTiernan has also shown in a recent, unique clinical trial, that postmenopausal, overweight or obese women who lost weight through a reduced calorie diet significantly lowered their levels of certain types of estrogen, testosterone, inflammation indicators and insulin—limiting their cancer risk. The good news is that the amount of weight loss required was modest and achievable for most people.

“This study,” she said, “is the first to show definitively that weight loss can move breast cancer risk factors in the right direction.”

“Our research suggests that losing just 5 percent or more of one’s body weight could cut by a quarter to a half the risk for the most common, estrogen-sensitive breast cancers,” McTiernan said. “The change in risk factors we observed has implications for other cancers and for other diseases such as heart disease and diabetes.”

Next-generation nutrition studies

McTiernan’s research has been key in establishing the Hutchinson Center as a leader in prevention, earning her a spot on a federal scientific advisory committee that developed the nation’s first-ever physical activity guidelines. These guidelines stressed that exercise reduced the risk of cancer and other diseases. She also received the prestigious Citation Award this year from the American College of Sports Medicine for her work on exercise and cancer.

Kratz tackles prevention from a different angle. He is studying how specific foods cause inflammation levels to rise and fall. Much of nutrition research uses so-called “observational studies” to evaluate whether diet increases disease risk. These studies ask people to report what they eat. They also track which diseases and health conditions those people develop and draw inferences between diet and health problems.

Most of today’s dietary guidelines were established using these observational studies, but they have flaws. Study participants often can’t remember what they ate or don’t want to admit to eating unhealthy things. Another problem is that eating behaviors are clustered—people who eat lots of red meat might often have other poor habits such as smoking, not exercising or drinking excessive alcohol.

“If a person has several potentially unhealthy habits and gets cancer, it’s hard to know exactly what contributed to their disease,” Kratz said.

Kratz is overcoming these problems by conducting interventional studies, which control a person’s entire diet. The Hutchinson Center’s Human Nutrition Lab prepares all of the food that study participants eat for anywhere from a few days to a couple of weeks.

Kratz’s team measures how participants respond to these diets, looking for changes in markers that contribute to ancer risk. One of Kratz’s current studies investigates how sweetened beverages such as regular soda impact levels of C-reactive protein (CRP)—which signals the presence of inflammation—in a person’s blood.

Kratz’s team gives the participants all their meals and snacks for eight days, including 30-60 ounces of beverages containing high fructose corn syrup or other sweeteners. Participants will repeat this three times, for a total of 24 days.

“Our pilot studies showed that some of these sweeteners could cause a significant increase in a person’s CRP levels,” Kratz said, “and if that happens in just eight days, imagine what it does over your entire life—it would have a substantial impact on your risk of developing many kinds of chronic diseases, including cancer.”

Kratz believes these intervention studies could reshape dietary guidelines to reflect new knowledge about which foods affect cancer risk. It’s all part of stopping obesity-related cancers before they strike. 

"Prevention is the best way to keep these cancers from getting out of hand,” Kratz said. “It helps people lead healthier, happier lives, and it’s a lot more cost-effective than treating these cancers once people get them—we simply couldn’t afford to do that.”

Science Editor Colleen Steelquist contributed to this article.


Obesity's link to cancer

Obesity is a risk factor for cancer, but that doesn’t mean all obese people will end up with cancer. The American Institute for
Cancer Research has linked obesity to 14 percent of all cancer deaths—and 20 percent of cancer deaths in women, with about 100,000 cancer deaths in the U.S. every year. One study showed that patients with a body mass index of at least 40 had cancer death rates 52 percent higher for men and 62 percent higher for women. The AICR has linked these cancers to excess body fat:

  • 49 percent of endometrial cancers: 20,700 cases per year
  • 35 percent  of esophageal cancers: 5,800 cases per year
  • 28 percent  of pancreatic cancers: 11,900 cases per year
  • 24 percent  of kidney cancers: 13,900 cases per year

What is inflammation?

The more scientists piece together the story of what causes cancer, the more evidence points to inflammation as one of the key villains. But it’s important to remember that, when it comes to human health, inflammation starts out as one of the good guys.

Inflammation is a key part of the healing process. It’s signaled by redness, swelling and other signs that your body has dispatched blood and immune cells to fight infections or heal injuries.

Problems can arise when inflammation isn’t a temporary response, but a chronic state.

Hutchinson Center researchers are learning that factors like obesity, poor diets and lack of exercise can trigger constant, low-grade inflammation.

Instead of healing the body, this inflammation causes progressive damage that is linked to a variety of health problems including heart disease, diabetes
and many cancers.

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