Reported by Peggy Vaughn
January 30, 2004
At a time when nearly two-thirds of the U.S. population is considered overweight or obese,
compelling evidence suggests that excess body weight is a risk factor for many cancers. However,
body weight is among many health and lifestyle related factors that play a role in cancer risk
and survival. The term "energy balance" describes the complex interaction of diet, physical
activity, and genetics, and may play an important role in cancer prevention and control.
This edition of Benchmarks sheds some light into the complexities of energy balance and cancer.
An interview with Rachel Ballard-Barbash, M.D., associate director of applied research in NCI's
Division of Cancer Control and Population Sciences, provides an overview of energy balance issues.
What exactly is meant by the term "energy balance?"
The classic definition of energy balance is the balance between energy taken in, generally
by food and drink, and energy expended. Energy expenditure is influenced by genetics, body
size and amount of muscle, and by physical activity. In addition, a minor part of energy expenditure
is from the thermal effects of food-different foods generate different amounts of energy when you eat
them. But it's not just a question of calories in versus calories out. While calories are probably the
most critical element in maintaining your energy balance, other factors in your diet such as how much
fiber or calcium you eat may influence your energy expenditure and how much muscle and fat you have.
How does energy balance relate to cancer risk?
We think it's important to look at this intersection of weight, physical activity, and diet and
how we manage those in life, since they all have the potential to influence cancer risk. Rather
than focusing solely on diet or physical activity, energy balance is a way of characterizing the
important interaction between these behaviors.
We commonly use BMI (Body Mass Index, a measure of body fat based on person's height and weight)
to calculate whether a person is overweight or obese. How have the national averages for BMI changed over the years?
Obesity is defined as a BMI (weight in kilograms divided by height in meters squared) over 30.
In the early 1960s, when the government first started tracking BMI in the population, only about
11 percent of men and 16 percent of women had a BMI over 30. Today, close to 30 percent of men and
35 percent of women are obese. Among African-American women, the rate of obesity is 50 percent. There's
also evidence that obesity is increasing markedly in adolescents and children. Rates are climbing among
African-American and Hispanic populations and among people with lower income, lower education, and fewer
resources to address it.
The media are reporting a national "obesity epidemic." Is that a fair characterization?
Two thirds of the U.S. adult population have BMI's over 25, and that is the level at which we believe the
health risks of cancer and other diseases increase. Actually, you could say obesity is endemic and affects
the majority of the population, since two thirds of the U.S. population is experiencing the health problem.
Is there some genetic basis for this increase in obesity?
In the U.S. today and in other developed countries, people live in an environment of plenty with few
undergoing starvation--other than self-imposed dieting. But many thousands of years ago, the first human
beings typically lived in an environment where starvation was common and periodic. Changes in the genetic
makeup of the most successful humans allowed them to survive during those periods of starvation. We call
that genetic trait "the thrifty gene." We think it supports a host of responses that tend to increase the
likelihood of people becoming obese in an environment of plenty. The physiological response of the thrifty
gene runs counter to remaining lean and has resulted in increases in hypertension, heart disease, diabetes,
and many cancers.
What basic research is NCI conducting to address energy balance?
Over the last several years, epidemiological research has established linkages between these health factors and
many cancers in large cohort or case-control studies looking at the effects of weight, diet, physical activity,
and cancer outcomes. A large body of literature suggests being overweight or obese increases the risk for
postmenopausal breast cancer, colon cancer, adenocarcinoma of the esophagus, endometrial cancer, renal cell
carcinoma, and several other cancers. Other studies have explored the mechanisms by which obesity may be
influencing cancer risk, including some basic animal and cell culture studies. Clinical intervention studies,
involving small groups of patients, have looked at the effect of specific diet, activity, and weight control
regimens to see how they influence cancer risk.
What research are we doing in the area of obesity prevention?
Most of the research at NCI and NIH on obesity has focused on understanding obesity, its causation, consequences,
and approaches to treatment. There has been very limited research to date on obesity prevention. However, one
interesting prevention model in cancer has been developed. It involves exposing animals in early or mid-life to
moderate calorie restriction of 20 to 30 percent of their normal intake, combined with a physical regimen of
running on treadmills. These studies examine longevity and what kind of tumors develop. Some of the animals are
at high risk for spontaneously developing tumors and some animals are exposed to carcinogens that increase their
risk. One important role of this type of animal research is that there is an ability to see if there are
differences across the life course.
What are some of the findings of those studies?
With calorie restriction or increases in physical activity, the animals become lean and not obese. The
animals that are lean live longer by as much as 20 to 30 percent and have fewer tumors. In the future,
we may try to cross animal models that are at risk of cancer and at risk of becoming obese to see if there
are interventions to improve their outcome. We would anticipate that in human populations there are humans
both at risk of becoming obese and developing cancer. That's why it's important to understand the interventions
that may work for humans with different risk profiles.
What cancers are most associated with a higher BMI or obesity?
Obesity is associated with colon, postmenopausal breast cancer, endometrial cancer, renal cell, esophageal
cancer and thyroid cancer in women. For any cancers, however, our general recommendation is that there's
good evidence that avoiding weight gain during adult life and having an active lifestyle can prevent cancer.
Is there a recommended level of activity to reduce cancer risk?
People should be doing moderate to vigorous physical activity at least 30 minutes a day, most days of the
week. That's associated with reducing risk for several cancers, particularly colon and breast cancer. However,
there's additional benefit observed with being more physically active than that-with benefits observed for up
to an hour a day of exercise. Because so few of the population exercises at these much higher levels it is
difficult to exactly measure the amount of additional benefit.
Can a person prevent cancer through improved energy balance?
There's good evidence the risk of colon cancer is halved by having an active lifestyle. That's a critical
message. The question of what specific diets are most beneficial in avoiding weight gain is less certain,
other than eating less calories than you burn in a day to avoid weight gain.. A plant-based diet is beneficial
in decreasing the risk for many cancers, particularly colon cancer. But there are many questions still about
the type of carbohydrate in the diet and if the glycemic index of foods may alter risk. Glycemic index is a
measure of how rapidly the carbohydrates you eat are converted into simple sugars. Complex carbohydrates with
higher amounts of fiber have a lower glycemic index, and may have a more beneficial effect on metabolism than
foods with a high glycemic index.
Does obesity play a role in prostate cancer?
Interestingly, there is no clear association of obesity with prostate cancer. However, one study has suggested
that men with a higher level of leptin, which is a hormone closely associated with the amount of body fat on a
person's body, have an increased risk of prostate cancer. So we don't think we the story is quite final yet in
terms of how body fat may influence prostate cancer.
Does obesity ever play a role in preventing cancer?
For some cancers, studies consistently indicate that being heavy is protective or associated with decreased
risk. This includes premenopausal breast cancer, head and neck cancers, and lung cancer. However, for the
smoking related cancers-head, neck and lung-once you control for smoking, which tends to reduce a person's
weight, the connection between weight and these cancers is removed.
So obesity may actually prevent breast cancer in premenopausal women?
Studies consistently show heavier women in the premenopausal period are at decreased risk of breast cancer.
We think this is the case because heavier women actually have changes in their hormonal metabolism and
experience fewer menstrual cycles. These changes result in lower exposure to estrogen and thus lower
risk of developing premenopausal breast cancer. Studies also suggest that your weight in your 20s and
30s does not increase your risk for postmenopausal breast cancer. It's the higher weight later in life
that increases your risk. However, given the overall evidence, it is best to maintain a healthy weight
and avoid excessive weight gain throughout your life to reduce your risk for cancer, as well as many other diseases.
What do we know about obesity and postmenopausal breast cancer?
During menopause, when the ovaries no longer produce estrogen, the source of estrogen is from testosterone
and other hormones from the adrenal glands that are converted into estrogen in the fat cells. So it's very
dependent on how much fat you have on the body as to how much estrogen you produce. Estrogen is a major
factor in postmenopausal breast cancer.
How do obesity and being overweight impact breast cancer prognosis?
Women who are heavier at time of diagnosis and have gained weight during their treatment are more likely to
have a reoccurrence of their breast cancer and to have worse survival. This varies by the estrogen receptor
status of the cancer. Being heavy, most likely because it increases stimulates estrogen production in the
body, appears to increase growth of estrogen receptor positive tumors.
What is the relationship between weight, hormone therapy (HT) and breast
cancer?
In the mid-1990s, we began looking at postmenopausal women who were on estrogen, and those who were not,
to see if the weight association with breast cancer differed by use of hormone therapy. These studies found
women who take estrogen are at an increased risk for breast cancer, but that heavy women in that group did
not have further increased risk. The evidence suggests that's because the amount of estrogen from HT is very
high, so the modest amount of estrogen contributed by fat cell production of estrogen in the postmenopausal
period does not change that risk to a measurable amount.
What about women who do not take HT?
It's a strikingly different picture for these women. Overall, there is a 50 percent increase of breast cancer
risk for all women that are heavy in the postmenopausal period. However, for the subgroup of women that have
never taken HRT, being heavy results in a 200 to 350 percent increase in risk-a 4 to7 fold increase compared
to women overall.
What is being done to specifically address the so-called obesity epidemic?
There's a renewed focus of attention in this area. Both the NIH and NCI are funding research to better
understand the effect of obesity on health outcomes and to better understand and treat obesity. In 2002,
NCI formed a group to identify research priorities in this area. The group identified three priority goals
for NCI research: 1) to understand the causes of adverse patterns of weight, physical activity, and diet; 2)
to define their contributions to cancer; and 3) to apply this knowledge to cancer prevention and control.
How will NCI research advance these goals?
We're trying to understand how obesity can interact over the entire lifetime to influence the cancer process,
to develop better measures of weight, diet, and physical activity. In order to improve cancer-related health
outcomes, particularly in high-risk populations, we need to do research to identity effective interventions at
the individual and population levels. For example, there may be something we could do at schools that would be
particularly effective to prevent this weight gain we're seeing in children. There's a need to focus on prevention
among high-risk groups, such as children, certain minorities and low-income groups. We're calling for more research
to build better health monitoring systems so we know what's happening at the local and national levels and in
high-risk groups.
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