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Workshop Summary
INTRODUCTION
Recent research suggests that obesity and excess weight can play a
prominent role in the incidence and progression of various cancers. Obe-
sity results from an energy imbalance—that is, energy intake that is higher
than energy expenditure—that could also influence the growth of cancers.
In addition, by generating hormones and growth factors, and by fostering
inflammation, fat tissue could directly fuel the growth of tumors, thereby
affecting cancer incidence, progression, recurrence, and survival rates.
Given the current obesity epidemic and an aging population more suscep-
tible to cancer, there is mounting concern about the role that obesity plays
in malignancies. There is also interest in exploring possible interventions
to break the obesity–cancer link, especially in patients already diagnosed
with cancer, who are at risk for cancer progression and recurrence and are
also more susceptible to developing new cancers. Cancer survivors cur-
rently number 12 million in the United States and are rapidly increasing
in number.
Recognizing the impact that current findings on obesity and cancer
could have on future cancer prevention and care, the National Cancer
Policy Forum (NCPF) of the Institute of Medicine (IOM) held a 2-day
workshop1 on “The Role of Obesity in Cancer Survival and Recurrence,”
1 This workshop was organized by an independent planning committee whose role was
1
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2 THE ROLE OF OBESITY IN CANCER
in Washington, DC, on October 31 and November 1, 2011. At the work-
shop, experts presented the latest clinical evidence on the obesity–cancer
link and the molecular mechanisms that might explain that link. Clinicians,
researchers, cancer survivors, and policy makers also discussed potential
interventions to counter the effects of obesity on cancer, and research and
policy measures needed to stem the rising tide of cancer mortality predicted
by an increasingly overweight and older population worldwide. More spe-
cifically, the workshop explored:
• The complex web of molecular mechanisms that underlie the
obesity–cancer link and whether it is obesity itself, the energy
imbalance that leads to obesity, or the molecular pathways that are
deregulated due to obesity, that increases the risk of cancer initiation
or progression;
• Clinical evidence of the obesity link to cancer incidence and out-
comes and study design issues that may affect the strength of that
evidence and its interpretation, as well as ways to design future stud-
ies to acquire the information needed to guide patient care;
• Potential interventions to counter or prevent obesity effects and/or
restore energy balance, including lifestyle measures, as well as drug
and surgical therapies;
• What to advise cancer patients about weight loss, diet, exercise, and
other measures to reduce their risk of cancer progression or recur-
rence, and the challenges in inducing healthy behaviors; and
• Policy suggestions related to research, education, and dissemination
of the findings on obesity and cancer, as well as what the private and
public sectors can do to help break the obesity–cancer link.
This document is a summary of the workshop. The views expressed
in this summary are those of the speakers and discussants, as attributed
to them, and are not the consensus views of workshop participants or the
members of the NCPF.
limited to identification of topics and speakers. This workshop summary was prepared by
the rapporteurs as a factual summary of the presentations and discussions that took place at
the workshop. Statements, recommendations, and opinions expressed are those of individual
presenters and participants, and are not necessarily endorsed or verified by the Forums or the
National Academies, and they should not be construed as reflecting any group consensus.
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3
WORKSHOP SUMMARY
OVERVIEW OF THE OBESITY–CANCER LINK
The ancient Greek medical practitioner Hippocrates anecdotally
reported the observation that a healthy balance of food intake and physi-
cal activity promotes good health. But it was not until the early part of the
20th century that researchers showed tumor cells transplanted into under-
fed mice did not grow as rapidly as in those fed more abundantly, noted
Wendy Demark-Wahnefried, chair of nutrition sciences at the University
of Alabama at Birmingham and chair of the workshop planning committee.
More recently, there has been an explosion of research on obesity
and cancer, with more than 2,000 papers on the topic published in the
scientific literature. An extensive 2007 review of published research found
convincing evidence to link obesity to the risk of endometrial, colorectal,
esophageal, kidney, and pancreatic cancer as well as to postmenopausal
breast cancer (World Cancer Reasearch Fund and American Institute for
Cancer Research, 2007). This review found more limited evidence linking
obesity to gallbladder or liver cancer, as well as accumulating evidence that
obesity is linked to the risk of non-Hodgkin’s lymphoma, ovarian cancer,
and aggressive prostate cancer. “There are important public health implica-
tions in these findings. Obesity is the second leading risk factor for cancer,”
stressed Dr. Susan Gapstur, vice president of epidemiology at the American
Cancer Society.
This is especially alarming considering that since the 1970s, the num-
ber of Americans becoming obese or overweight has steadily risen; they now
comprise more than two-thirds of the population. The obesity epidemic is
also spreading internationally; the World Health Organization estimates
that more than 1.5 billion adults worldwide are overweight or obese. “The
obesity epidemic is not just a U.S. problem—it’s a worldwide problem,”
noted Dr. Gapstur. However, there is debate over why obesity is increasing
in prevalence, with several reasons posited by experts, including the rising
consumption of sugar-sweetened beverages, an increase in portion size, and
the decline in physical activity, in part due to increased automation. “I don’t
think we can say there is any one sole factor that has led to that change,” said
Dr. Rachel Ballard-Barbash, who serves as the associate director of applied
research in the Division of Cancer Control and Population Sciences at the
National Cancer Institute. Dr. Gapstur agreed, noting “there’s not one
simple answer because it gets back to that concept of energy balance.” (See
Box 1 for a discussion of energy balance.)
The increasing incidence of breast cancer in developing countries
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4 THE ROLE OF OBESITY IN CANCER
BOX 1
Energy Balance and Cancer Risk
Dr. Wendy Demark-Wahnefried gave a brief overview of energy
balance and what factors influence it and how it influences cancer risk.
She noted that the energy balance in a person’s body is determined
by energy intake from the diet, which can be modified by ingestion and
absorption, balanced by the total calories expended. Typically, about 60
to 75 percent of energy is expended by maintaining the resting metabolic
rate, 5 to 10 percent is expended as the energy needed to digest food,
and 15 to 30 percent is expended through physical exercise (Figure 1).
Dr. Demark-Wahnefried also noted that a gastric bypass or a lap
band will induce a shift in energy balance by reducing calorie intake.
The main dispeller of energy is resting metabolic rate, which is driven,
in part, by lean body mass. As people age, she noted, they expend less
energy because they do not have as much muscle mass. Chemotherapy
and other cancer treatments can also decrease lean body mass. Resting
metabolic rate is also driven by the balance of the external temperature
with the body’s internal temperature, with more energy expended when
the external temperature drops below 78 degrees Fahrenheit. Disease
can affect body temperature as well.
is thought to reflect the increase in obesity in these nations, added
Dr. Ballard-Barbash. Dr. Nathan Berger, a professor of medicine and direc-
tor of the Center for Science, Health, and Society at the Case Western
Reserve University School of Medicine, added that “the convergence of
obesity and aging is the perfect storm or tsunami in terms of increasing the
overall incidence of cancer.”
But obesity does not appear to have a uniform effect on all types of
cancers, nor to affect cancer risk the same in men and women. One study
found that obesity increases the risk of dying from all cancers by about
52 percent in men, but nearly doubled the risk of dying from any type of
cancer in women (Calle et al., 2003). For some cancers, such as liver cancer,
obesity was linked to about a five-fold increased risk of cancer mortality in
both sexes. In contrast, the association between obesity and colon cancer
mortality is not equally strong in women and men, perhaps because body
mass index (BMI) is a better measure of abdominal fat in men than women,
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5
WORKSHOP SUMMARY
Several researchers have attempted to assess how the various
components of energy balance affect cancer risk. One study showed that
calorie restriction consistently lowers the risk of cancer mortality across
several species, from the mouse to the cow (Hursting et al., 2003). Stud-
ies on the effects of physical exercise on cancer risk are less consistent,
Dr. Demark-Wahnefried said, although a few studies suggest that when
energy intake is kept constant, animals that exercise more have less
cancer progression. However, one study found that expression of several
genes is altered when mice are placed on caloric restriction, but there
are relatively few changes in gene expression when caloric intake is kept
stable while mice are exercised (Padovani et al., 2009).
Dr. Demark-Wahnefried stressed “the need to disentangle effects of
caloric restriction and increased physical activity, as well as obesity. Can-
cer is complex and energy balance is complex. It’s really difficult to make
a change in one factor without impacting another.” As she noted when
people exercise a lot, their appetite tends to increase and leads them to
eat more, whereas there is some evidence that moderate amounts of
physical activity can actually suppress appetite. “So if you are going to
conduct a physical activity intervention, then it is important to measure
and control for dietary intake,” Dr. Demark-Wahnefried said.
or because of hormonal factors that are protective, Dr. Gapstur pointed out
(Box 2).
Obesity-related breast cancer risk also varies by menopausal status.
Increasing BMI levels are linked to a lower incidence of breast cancer in
premenopausal women, but a greater incidence of breast cancer in post-
menopausal women, Dr. Gapstur said, for reasons that are not yet clearly
defined. Obesity’s influence on prostate cancer risk also varies. Although
obesity is associated with a lower incidence of prostate cancer, studies sug-
gest that obesity is linked to a greater risk of being diagnosed with a more
aggressive form of prostate cancer, and studies have consistently shown that
obesity substantially increases the risk of dying from prostate cancer. “These
data suggest that one shoe doesn’t fit all, and it may be very important to
separate the different disease types,” she said.
Growing evidence also indicates that obesity during childhood can
increase the risk of childhood cancers, such as leukemia, and young-onset
brain tumors, Dr. Ballard-Barbash noted. “This is an issue that is urgent
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6 THE ROLE OF OBESITY IN CANCER
ENERGY BALANCE
Total Energy Expenditure (TEE)
Energy Intake
(Calories Out)
(Calories In)
Modified by inges on
Res ng Metabolic Rate (RMR)
and/or absorp on.
(energy needed to maintain body
func on at rest, ~ 60-75% TEE)
Thermic Effect of Food
(energy for diges on/metabolism 5-10% TEE)
Physical Ac vity
(15-30% TEE)
FIGURE 1 Energy editable
Figure 1-5, balance. Weight maintenance occurs when energy input equals
energy expenditure, with gains and losses occurring when there is an imbalance. A
gain of one pound occurs when approximately 3,500 calories are consumed in excess
of energy needs. For most individuals, resting metabolic rate (RMR) comprises the
major component of energy expenditure, accounting for 60-75 percent of energy needs
(IOM, 2005; Pi-Sunyer, 2000). Resting metabolic rate is largely governed by lean tissue,
which has a higher metabolic rate than adipose tissue. Neoplastic tissue also may have a
higher metabolic rate, though a study of 200 cancer patients compared to 200 healthy
controls found that metabolic rate was highly variable among cancer patients (50-175
percent of predicted values) and greatly influenced by tumor stage and site (Knox et
al., 1983). Speculation also exists that RMR may be influenced by various cytokines,
though more research is necessary (Pi-Sunyer, 2000). The Thermic Effect of Food, also
known as Specific Dynamic Action, is the energy needed for digestion and metabolism
of food—transient energy needs that go above and beyond normal metabolism. The
Thermic Effect of Food accounts for only 5-10 percent of energy needs and is dependent
upon the magnitude of dietary intake, and also may be influenced by the consumption
of specific foods or food-related substances. For example, tea, capsaicin, and caffeine
may increase metabolism even further (Bell and Goodrick, 2002), though more studies
are needed to determine if these transient increases are clinically meaningful. Physical
activity comprises the third component of energy expenditure and for individuals living
in the developed world, usually accounts for 15-30 percent of energy needs. The energy
expended for physical activity is the most modifiable component of energy expenditure.
Furthermore, given the potential of exercise (especially resistance training) to increase
lean body mass, physical activity also may act indirectly to increase RMR.
SOURCE: Demark-Wahnefried presentation (October 31, 2011). Reprinted with per-
mission from Wendy Demark-Wahnefried.
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7
WORKSHOP SUMMARY
BOX 2
How Obesity Is Measured
There are several assessments of overweight and obesity;
the most common is body mass index (BMI). BMI is weight (kg)/
height squared (m2). It is frequently used in studies because it is a
single measure that can be determined easily, Dr. Susan Gapstur
pointed out, and is comparable among studies. Below are the
World Health Organization criteria for overweight and obesity:
• Underweight = BMI < 18.5 kg/m2
• Normal weight = BMI 18.5-24.9 kg/m2
• Overweight = BMI 25.0-29.9 kg/m2
• Obese = BMI 30+ kg/m2
An individual’s body fat distribution can also be assessed with
anthropometric methods such as measurements of waist and hip
circumference or the ratio of the two, or techniques such as air
displacement or bioelectrical impedance to determine percentage
of body fat. BMI correlates well with percentage of body fat in the
average population, according to Dr. Gapstur.
for our children, even beyond what the effect will be in their adult lives,”
she said.
MOLECULAR MECHANISMS
The variability in how obesity affects the incidence, progression, or
mortality of various cancers suggests that these effects derive from multiple
mechanisms, which animal research supports. This research implies a web of
interacting hormones, growth factors, cytokines, and inflammation media-
tors that promote tumor initation and growth.
As Dr. Berger noted, an excess of nutrients causes an imbalance in
energy. This imbalance causes oxidative stress and abnormalities of fatty acid
metabolism that foster inflammation and insulin resistance (Figure 2). This
results in a number of processes that underlie cancer initiation and promo-
tion, including DNA damage, cell division, delayed cell death, an increase
in blood vessel formation, and cell migration (Figure 3).
The complex interactions between all the obesity-activated hormones
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8 THE ROLE OF OBESITY IN CANCER
FIGURE 2 An integrative view of obesity.
SOURCE: Berger presentation (October 31, 2011). Adapted from Wisse et al. (2007).
An Integrative View of Obesity. Science 318:928-929. Reprinted with permission from
AAAS and Nathan Berger.
and growth factors make it difficult to pinpoint targets for interventions.
“It’s important to remember that if you are directing your therapy at leptin,
for example, or at reducing insulin levels, all these other factors are going on
simultaneously. If we really are going to attack the obesity–cancer link, it’s
going to require attacking many of these components, if not all, simultane-
ously,” Dr. Berger said.
Dr. Berger stressed the crosstalk that occurs among several different
obesity-activated pathways leading to cancers, as well as the cellular signal-
ing that occurs among fat tissue, the immune system, and cancer cells. Dr.
Derek LeRoith, director of the Metabolism Institute and chief of Endocri-
nology, Diabetes, and Bone Diseases at the Mount Sinai School of Medi-
cine, agreed, pointing out that animal models can help researchers delineate
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FIGURE 3 Putative factors involved in obesity-related carcinogenesis. Factors denoted in red text are core features in the Metabolic Syndrome.
Factors denoted in blue text are additional features that may also be components of the Metabolic Syndrome.
NOTE: BMI = body mass index; CRP = C-reactive protein; FFA = free fatty acid; IGF = insulin-like growth factor; IGFBPs = insulin-like growth
factor binding proteins; IL = interleukin; MAC = macrophages; MCP = monocyte chemotactic protein; mito = mitochondria; PAI = plasminogen
activator inhibitor; PGE = prostaglandin; ROS = reactive oxygen species; SHBG = sex hormone binding globulin; TG = triglycerides; TNF = tumor
necrosis factor; VEGF = vascular epithelial growth 1-2, xed image
Figure factor.
9
SOURCE: Berger presentation (October 31, 2011). Adapted from Nock and Berger, 2010. Reprinted with permission from Nathan Berger.
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10 THE ROLE OF OBESITY IN CANCER
which molecules and pathways underlie the obesity–cancer link, but that
those individual compounds or pathways need to be kept in context. “It’s
all of them, and hitting one may be insufficient,” he said, adding that many
pharmaceutical companies are trying to develop combination therapies that
target two or more key molecules in different pathways simultaneously.
Some of these molecular pathways could foster cancer initiation or
promotion, or both. For example, Dr. Pamela Goodwin, senior scientist and
Marvelle Koffler Chair in Breast Cancer Research at Mount Sinai Hospital,
noted that obesity is linked to an increased risk of breast cancer progression,
but not initiation in premenopausal women. Obese premenopausal women
actually have a lower incidence of breast cancer than premenopausal women
of normal weight, perhaps because of abnormal estrogen metabolism and/
or other factors related to having an energy imbalance, Dr. Gapstur pointed
out. Dr. LeRoith suggested the low testosterone of obese men may protect
them from developing prostate cancer, but once they develop this tumor,
obesity and the excessive insulin production it causes could foster the
aggressive growth and metastasis of prostate cancer. Dr. Stephen Hursting,
professor at the University of Texas at Austin, and MD Anderson Cancer
Center, pointed out that studies using a variety of animal models support
the premise that obesity fosters cancer promotion, but the link between
obesity and cancer initiation is more tenuous.
Dr. Berger noted that the heightened metabolism of fatty acids that
occurs in obese individuals might increase DNA damage due to oxidation.
But little to no evidence shows that this DNA damage triggers a malignant
transformation, even though DNA damage in general has been shown to
cause cancer. He questioned whether obesity actually fosters the initiation
of cancer, or rather causes cancer promotion so that the cancer is diagnosed
earlier in life.
“Data exist to support the latter for pancreatic cancer (Harvey, 2011),
but for none of the other cancers. This is a really important question,
because if obesity is causing one of the initial mutations, then we need to
treat it early and think about how to block the mutations. But if obesity
is really causing progression, then there will be whole different strategy to
deal with it,” Dr. Berger said. Dr. John DiGiovanni, professor of pharmacol-
ogy, toxicology, and nutrition sciences at the University of Texas at Austin,
noted that the AKT-mTOR pathway that is activated in obese animals is
linked to increased risk of developing a cancer, as well as to the progression
of many cancers.
There was general agreement, however, that cancer is a disorder whose
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11
WORKSHOP SUMMARY
hallmark is abnormal regulation of the growth and survival of cells, and
that fat cells generate many hormones, growth factors, and cytokines that
can disrupt regulation of cell growth and survival. The key mechanistic
molecular factors discussed at the workshop were estrogen, insulin, insulin-
like growth factor 1 (IGF-1), leptin, adiponectin, and adipokinase, as well
as several mediators of inflammation.
Estrogen
Seventy percent of all breast cancer patients are postmenopausal
women. Most of the estrogen produced in postmenopausal women is
derived from fat tissue via the enzyme aromatase, which converts adrenal
androgens into estrogen. The more fat tissue there is, the greater the levels
of estrogen produced and in circulation. Such estrogen can fuel the growth
of estrogen receptor–positive breast cancers. Studies show that mice made
obese by being fed a high-fat diet and then inoculated with breast cancer
cells had significantly greater tumor growth rates than mice similarly inocu-
lated, but fed a normal diet (Sabnis et al., 2009). When inoculated obese
mice were given an aromatase inhibitor, the tumor growth rate was mark-
edly inhibited, reported Dr. Angela Brodie, professor of pharmacology and
experimental therapeutics at the Marlene and Stewart Greenbaum Cancer
Center of the University of Maryland School of Medicine.
Clinical studies confirm that circulating estradiol levels are linked to
risk of recurrence of breast cancer, but Dr. Goodwin pointed out this mech-
anism does not explain the association of obesity with premenopausal breast
cancer outcomes or with estrogen receptor–negative breast cancer outcomes
(Pierce et al., 2007a). Dr. Gapstur added that it also does not explain why
estrogen is linked to both pre- and postmenopausal endometrial cancer risk
(Reeves et al., 2007).
Insulin
Dr. Goodwin and others have data to suggest that another factor mak-
ing obese women more susceptible to breast cancer recurrence and death is
the higher than normal insulin level that is often linked to obesity. Increases
in BMI correlate closely with increases in fasting insulin levels in the non-
diabetic population, Dr. Goodwin noted, and greater levels of insulin are
linked to increased risk of distant recurrence and death in breast cancer
patients (Gallagher and LeRoith, 2011; Goodwin et al., 2002).
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70 THE ROLE OF OBESITY IN CANCER
international cancer community models many of their policies according
to what ASCO advocates. Dr. Wadden advocated for more educational and
policy efforts being made to prevent obesity in the general population as
well. “Treatment alone is clearly not the answer to the obesity epidemic. We
have to do more to prevent this disorder,” he said.
Dr. Partridge stressed that obesity is an interesting disease because in
addition to its molecular basis, it is impacted by individual behavior, and by
family, workplace, or community influences on that behavior. “I can visual-
ize a system’s biomedicine approach to obesity in which you have the basic
scientists, the behaviorists, the epidemiologists, and the political scientists
working together in transdisciplinary teams with excellent informatics that
links all that together, so you can begin to tease out the important factors
at each level needed to make some progress,” he said.
Mr. Kean suggested reaching out to experts who can frame the obesity
and cancer policy issues within the context of the economy and jobs or
other high-priority topics that are more likely to garner the interest of poli-
ticians who can influence obesity policies. He also suggested collaborating
with the IOM Evidence Communication Innovation Collaborative, which
is currently assessing how best to communicate evidence to patients and
the public at large.
Dr. Morgan Downey, of the Downey Obesity Report, stressed the genetic
and epigenetic components of obesity and cautioned that such factors be
considered when devising health or workplace policies related to the dis-
order. He said that according to obesity researcher Jeffrey Freidman, body
weight is as heritable as height (Friedman, 2004), so obesity is different
from a behavior such as smoking, which is more likely to be susceptible
to financial disincentives or penalties. He said that some workplaces and
insurers and even the Affordable Care Act are suggesting placing similar
penalties on people who are overweight and obese. “We have to be careful
because the types of interventions that were successful in cancer prevention
via smoking I don’t think are going to prove very effective in long-term
obesity reduction.”
WRAPPING UP
Dr. Wahnefried-Demark provided some closing remarks, noting that
growing evidence from both clinical and animal studies shows that obesity
increases the risk of cancer incidence, recurrence after treatment, progres-
sion, and cancer death for many organ sites. This is a significant public
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71
WORKSHOP SUMMARY
health concern given that an obesity epidemic is currently spreading world-
wide, and obesity is the second leading risk factor for cancer incidence. Hor-
mones, growth factors, and inflammation may underlie the mechanisms by
which obesity increases cancer risk, with animal and human study results
consistently suggesting specific interacting mechanistic pathways that vary
by cancer subtype.
Key molecules in those pathways could serve as targets for drugs aimed
at preventing cancer or cancer recurrence or progression. There is grow-
ing evidence that lifestyle measures, such as reducing weight, maintaining
a healthy diet, and increasing physical activity could also lower cancer
risk. Most of that evidence is observational and would be strengthened
by randomized clinical trials. However, routine measurements of obesity
indicators in clinical trials would aid researchers’ attempts to document
the benefits of various interventions in stemming obesity and its impact
on cancer risk.
In the meantime, more education of oncologists, dietitians, primary
care physicians, and other healthcare practitioners who work with cancer
survivors and better dissemination of what is known about obesity’s influ-
ence on the risk of cancer recurrence, progression, and mortality, and ways
to ameliorate that risk could be beneficial.
Reimbursement by health insurers for obesity treatments, including
weight loss programs, and more involvement of industry and schools in pro-
moting policies that help prevent obesity might also have a positive impact,
not just on cancer incidence, but on the well-being of cancer patients.
REFERENCES
Abdelmalek, M. F., A. Suzuki, C. Guy, A. Unalp-Arida, R. Colvin, R. J. Johnson, and A. M.
Diehl. 2010. Increased fructose consumption is associated with fibrosis severity in
patients with nonalcoholic fatty liver disease. Hepatology 51(6):1961-1971.
Abrahamson, P. E., M. D. Gammon, M. J. Lund, J. A. Britton, S. W. Marshall, E. W. Flagg,
P. L. Porter, L. A. Brinton, J. W. Eley, and R. J. Coates. 2006. Recreational physical
activity and survival among young women with breast cancer. Cancer 107(8):1777-
1785.
Ackermann, R. T., E. A. Finch, E. Brizendine, H. Zhou, and D. G. Marrero. 2008.
Translating the Diabetes Prevention Program into the community. The DEPLOY Pilot
Study. Am J Prev Med 35(4):357-363.
Adams, T. D., R. E. Gress, S. C. Smith, R. C. Halverson, S. C. Simper, W. D. Rosamond,
M. J. Lamonte, A. M. Stroup, and S. C. Hunt. 2007. Long-term mortality after gastric
bypass surgery. N Engl J Med 357(8):753-761.
OCR for page 72
72 THE ROLE OF OBESITY IN CANCER
Aggarwal, B. B., A. Kumar, and A. C. Bharti. 2003. Anticancer potential of curcumin:
preclinical and clinical studies. Anticancer Res 23(1A):363-398.
Baumgartner, K. B., W. C. Hunt, R. N. Baumgartner, D. D. Crumley, F. D. Gilliland,
A. McTiernan, L. Bernstein, and R. Ballard-Barbash. 2004. Association of body
composition and weight history with breast cancer prognostic markers: Divergent
pattern for Hispanic and non-Hispanic White women. Am J Epidemiol 160(11):
1087-1097.
Behan, J. W., J. P. Yun, M. P. Proektor, E. A. Ehsanipour, A. Arutyunyan, A. S. Moses, V. I.
Avramis, S. G. Louie, A. Butturini, N. Heisterkamp, and S. D. Mittelman. 2009.
Adipocytes impair leukemia treatment in mice. Cancer Res 69(19):7867-7874.
Bell, S. J., and G. K. Goodrick. 2002. A functional food product for the management of
weight. Crit Rev Food Sci Nutr 42(2):163-178.
Bodmer, M., C. Meier, S. Krahenbuhl, S. S. Jick, and C. R. Meier. 2010. Long-term
metformin use is associated with decreased risk of breast cancer. Diabetes Care 33(6):
1304-1308.
Bond, D. S., J. M. Jakicic, J. L. Unick, S. Vithiananthan, D. Pohl, G. D. Roye, B. A. Ryder,
H. C. Sax, and R. R. Wing. 2010. Pre- to postoperative physical activity changes in
bariatric surgery patients: Self report vs. objective measures. Obesity 18(12):2395-2397.
Bosco, J. L., S. Antonsen, H. T. Sorensen, L. Pedersen, and T. L. Lash. 2011. Metformin and
incident breast cancer among diabetic women: A population-based case-control study
in Denmark. Cancer Epidemiol Biomarkers Prev 20(1):101-111.
Brown, D. A., K. W. Hance, C. J. Rogers, L. B. Sansbury, P. S. Albert, G. Murphy, A. O.
Laiyemo, Z. Wang, A. J. Cross, A. Schatzkin, M. Danta, P. Srasuebkul, J. Amin, M.
Law, S. N. Breit, and E. Lanza. 2011. Serum Macrophage Inhibitory Cytokine-1
(MIC-1/GDF15): A potential screening tool for the prevention of colon cancer? Cancer
Epidemiol Biomarkers Prev 21(2):337-346.
Caan, B. J., M. L. Kwan, G. Hartzell, A. Castillo, M. L. Slattery, B. Sternfeld, and E. Weltzien.
2008. Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis
among women with early stage breast cancer. Cancer Causes Control 19(10):1319-1328.
Calle, E. E., C. Rodriguez, K. Walker-Thurmond, and M. J. Thun. 2003. Overweight,
obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N
Engl J Med 348(17):1625-1638.
Cao, Y., and J. Ma. 2011. Body mass index, prostate cancer-specific mortality, and
biochemical recurrence: A systematic review and meta-analysis. Cancer Prev Res (Phila)
4(4):486-501.
Checkley, L. A., O. Rho, T. Moore, S. Hursting, and J. DiGiovanni. 2011. Rapamycin is a
potent inhibitor of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.
Cancer Prev Res (Phila) 4(7):1011-1020.
Chen, J. 2011. Multiple signal pathways in obesity-associated cancer. Obes Rev 12(12):
1063-1070.
Chen, X., W. Lu, W. Zheng, K. Gu, C. E. Matthews, Z. Chen, Y. Zheng, and X. O. Shu.
2011. Exercise after diagnosis of breast cancer in association with survival. Cancer Prev
Res (Phila) 4(9):1409-1418.
Cheville, A. L., A. B. Kornblith, and J. R. Basford. 2011. An examination of the causes for
the underutilization of rehabilitation services among people with advanced cancer. Am
J Phys Med Rehabil 90(5 Suppl 1):S27-S37.
OCR for page 73
73
WORKSHOP SUMMARY
Chlebowski, R. T., M. Pettinger, M. L. Stefanick, B. V. Howard, Y. Mossavar-Rahmani, and
A. McTiernan. 2004. Insulin, physical activity, and caloric intake in postmenopausal
women: breast cancer implications. J Clin Oncol 22(22):4507-4513.
Christou, N. V., M. Lieberman, F. Sampalis, and J. S. Sampalis. 2008. Bariatric surgery
reduces cancer risk in morbidly obese patients. Surg Obes Relat Dis 4(6):691-695.
Colbert, L. H., V. Mai, S. N. Perkins, D. Berrigan, J. A. Lavigne, H. H. Wimbrow, W. G.
Alvord, D. C. Haines, P. Srinivas, and S. D. Hursting. 2003. Exercise and intestinal
polyp development in APCMin mice. Med Sci Sports Exerc 35(10):1662-1669.
Colbert, L. H., V. Mai, J. A. Tooze, S. N. Perkins, D. Berrigan, and S. D. Hursting.
2006. Negative energy balance induced by voluntary wheel running inhibits polyp
development in APCMin mice. Carcinogenesis 27(10):2103-2107.
Courneya, K. S., C. M. Booth, S. Gill, P. O’Brien, J. Vardy, C. M. Friedenreich, H. J. Au,
M. D. Brundage, D. Tu, H. Dhillon, and R. M. Meyer. 2008. The Colon Health and
Life-Long Exercise Change Trial: A randomized trial of the National Cancer Institute
of Canada Clinical Trials Group. Curr Oncol 15(6):279-285.
Craft, L. L., E. H. Vaniterson, I. B. Helenowski, A. W. Rademaker, and K. S. Courneya.
2012. Exercise effects on depressive symptoms in cancer survivors: A systematic review
and meta-analysis. Cancer Epidemiol Biomarkers Prev 21(1):3-19.
Cufi, S., A. Vazquez-Martin, C. Oliveras-Ferraros, B. Martin-Castillo, J. Joven, and J. A.
Menendez. 2010. Metformin against TGFbeta-induced epithelial-to-mesenchymal
transition (EMT): From cancer stem cells to aging-associated fibrosis. Cell Cycle
9(22):4461-4468.
Currie, C. J., C. D. Poole, and E. A. Gale. 2009. The influence of glucose-lowering therapies
on cancer risk in type 2 diabetes. Diabetologia 52(9):1766-1777.
Decensi, A., M. Puntoni, P. Goodwin, M. Cazzaniga, A. Gennari, B. Bonanni, and S.
Gandini. 2010. Metformin and cancer risk in diabetic patients: A systematic review
and meta-analysis. Cancer Prev Res (Phila) 3(11):1451-1461.
Demark-Wahnefried, W., B. Peterson, C. McBride, I. Lipkus, and E. Clipp. 2000. Current
health behaviors and readiness to pursue life-style changes among men and women
diagnosed with early stage prostate and breast carcinomas. Cancer 88(3):674-684.
Dignam, J. J., B. N. Polite, G. Yothers, P. Raich, L. Colangelo, M. J. O’Connell, and N.
Wolmark. 2006. Body mass index and outcomes in patients who receive adjuvant
chemotherapy for colon cancer. J Natl Cancer Inst 98(22):1647-1654.
Duggan, C., M. L. Irwin, L. Xiao, K. D. Henderson, A. W. Smith, R. N. Baumgartner, K. B.
Baumgartner, L. Bernstein, R. Ballard-Barbash, and A. McTiernan. 2011. Associations
of insulin resistance and adiponectin with mortality in women with breast cancer. J
Clin Oncol 29(1):32-39.
Ewertz, M., M. B. Jensen, K. A. Gunnarsdottir, I. Hojris, E. H. Jakobsen, D. Nielsen, L. E.
Stenbygaard, U. B. Tange, and S. Cold. 2011. Effect of obesity on prognosis after early-
stage breast cancer. J Clin Oncol 29(1):25-31.
Ferrer, R. A., T. B. Huedo-Medina, B. T. Johnson, S. Ryan, and L. S. Pescatello. 2011.
Exercise interventions for cancer survivors: A meta-analysis of quality of life outcomes.
Ann Behav Med 41(1):32-47.
OCR for page 74
74 THE ROLE OF OBESITY IN CANCER
Flum, D. R., S. H. Belle, W. C. King, A. S. Wahed, P. Berk, W. Chapman, W. Pories, A.
Courcoulas, C. McCloskey, J. Mitchell, E. Patterson, A. Pomp, M. A. Staten, S. Z.
Yanovski, R. Thirlby, and B. Wolfe. 2009. Perioperative safety in the longitudinal
assessment of bariatric surgery. N Engl J Med 361(5):445-454.
Foster, G. D., H. R. Wyatt, J. O. Hill, A. P. Makris, D. L. Rosenbaum, C. Brill, R. I. Stein,
B. S. Mohammed, B. Miller, D. J. Rader, B. Zemel, T. A. Wadden, T. Tenhave, C. W.
Newcomb, and S. Klein. 2010. Weight and metabolic outcomes after 2 years on a low-
carbohydrate versus low-fat diet: A randomized trial. Ann Intern Med 153(3):147-157.
Freedland, S. J., K. A. Grubb, S. K. Yiu, E. B. Humphreys, M. E. Nielsen, L. A. Mangold,
W. B. Isaacs, and A. W. Partin. 2005. Obesity and risk of biochemical progression
following radical prostatectomy at a tertiary care referral center. J Urol 174(3):919-922.
Friedman, J. M. 2004. Modern science versus the stigma of obesity. Nature Medicine 10(6):
563-569.
Gallagher, E. J., and D. LeRoith. 2011. Minireview: IGF, insulin, and cancer. Endocrinology
152(7):2546-2551.
Gans, K. M., E. Ross, C. W. Barner, J. Wylie-Rosett, J. McMurray, and C. Eaton. 2003.
REAP and WAVE: New tools to rapidly assess/discuss nutrition with patients. J Nutr
133(2):556S-562S.
Goodwin, P. J., M. Ennis, K. I. Pritchard, M. E. Trudeau, J. Koo, Y. Madarnas, W. Hartwick,
B. Hoffman, and N. Hood. 2002. Fasting insulin and outcome in early-stage breast
cancer: Results of a prospective cohort study. J Clin Oncol 20(1):42-51.
Goodwin, P. J., J. A. Ligibel, and V. Stambolic. 2009. Metformin in breast cancer: Time for
action. J Clin Oncol 27(20):3271-3273.
Goodwin, P. J., M. Ennis, K. I. Pritchard, M. E. Trudeau, J. Koo, S. K. Taylor, and N. Hood.
2012. Insulin- and obesity-related variables in early-stage breast cancer: Correlations
and time course of prognostic associations. J Clin Oncol 30(2):164-171.
Harrison, D. E., R. Strong, Z. D. Sharp, J. F. Nelson, C. M. Astle, K. Flurkey, N. L. Nadon,
J. E. Wilkinson, K. Frenkel, C. S. Carter, M. Pahor, M. A. Javors, E. Fernandez,
and R. A. Miller. 2009. Rapamycin fed late in life extends lifespan in genetically
heterogeneous mice. Nature 460(7253):392-395.
Harvey, A. E. 2011. Energy balance, inflammation, and tumor progression: The role of NF-
[kappa]B. http://repositories.lib.utexas.edu/handle/2152/ETD-UT-2011-05-3279
(accessed January 30, 2012).
Harvey, A. E., L. M. Lashinger, and S. D. Hursting. 2011. The growing challenge of obesity
and cancer: an inflammatory issue. Ann N Y Acad Sci 1229:45-52.
Harvey-Berino, J., D. West, R. Krukowski, E. Prewitt, A. VanBiervliet, T. Ashikaga, and J.
Skelly. 2010. Internet delivered behavioral obesity treatment. Prev Med 51(2):123-128.
Haydon, A. M., R. J. Macinnis, D. R. English, and G. G. Giles. 2006. Effect of physical
activity and body size on survival after diagnosis with colorectal cancer. Gut 55(1):
62-67.
Hecker, P. A., K. M. O’Shea, T. F. Galvao, B. H. Brown, and W. C. Stanley. 2011. Role of
adiponectin in the development of high fat diet-induced metabolic abnormalities in
mice. Horm Metab Res 43(2):100-105.
Heymsfield, S. B., C. A. van Mierlo, H. C. van der Knaap, M. Heo, and H. I. Frier. 2003.
Weight management using a meal replacement strategy: Meta and pooling analysis from
six studies. Int J Obes Relat Metab Disord 27(5):537-549.
OCR for page 75
75
WORKSHOP SUMMARY
Holick, C. N., P. A. Newcomb, A. Trentham-Dietz, L. Titus-Ernstoff, A. J. Bersch, M. J.
Stampfer, J. A. Baron, K. M. Egan, and W. C. Willett. 2008. Physical activity and
survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev
17(2):379-386.
Holmes, M. D., W. Y. Chen, D. Feskanich, C. H. Kroenke, and G. A. Colditz. 2005. Physical
activity and survival after breast cancer diagnosis. JAMA 293(20):2479-2486.
Hursting, S. D., and N. A. Berger. 2010. Energy balance, host-related factors, and cancer
progression. J Clin Oncol 28(26):4058-4065.
Hursting, S. D., J. A. Lavigne, D. Berrigan, S. N. Perkins, and J. C. Barrett. 2003. Calorie
restriction, aging, and cancer prevention: Mechanisms of action and applicability to
humans. Annu Rev Med 54:131-152.
Imayama, I., C. M. Alfano, A. Kong, K. E. Foster-Schubert, C. E. Bain, L. Xiao, C. Duggan,
C. Y. Wang, K. L. Campbell, G. L. Blackburn, and A. McTiernan. 2011. Dietary
weight loss and exercise interventions effects on quality of life in overweight/obese
postmenopausal women: A randomized controlled trial. Int J Behav Nutr Phys Act 8:118.
IOM (Institute of Medicine). 2005. Dietary reference intakes for energy, carbohydrate, fiber,
fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington, DC:
The National Academies Press.
IOM. 2011a. Early childhood obesity prevention policies. Washington, DC: The National
Academies Press.
IOM. 2011b. Legal strategies in childhood obesity prevention: Workshop summary. Washington,
DC: The National Academies Press.
IOM. 2011c. Leveraging food technology for obesity prevention and reduction efforts: Workshop
summary. Washington, DC: The National Academies Press.
IOM. 2012a. Mesuring progress in obesity prevention: Workshop report. Washington, DC: The
National Academies Press.
IOM. 2012b. Accelerating progress in obesity prevention: Solving the weight of the nation.
Washington, DC: The National Academies Press.
IOM. 2012c. Alliances for obesity prevention: Finding common ground: Workshop summary.
Washington, DC: The National Academies Press.
Irwin, M. L., A. McTiernan, L. Bernstein, F. D. Gilliland, R. Baumgartner, K. Baumgartner,
and R. Ballard-Barbash. 2005. Relationship of obesity and physical activity with
C-peptide, leptin, and insulin-like growth factors in breast cancer survivors. Cancer
Epidemiol Biomarkers Prev 14(12):2881-2888.
Irwin, M. L., A. W. Smith, A. McTiernan, R. Ballard-Barbash, K. Cronin, F. D. Gilliland,
R. N. Baumgartner, K. B. Baumgartner, and L. Bernstein. 2008. Influence of pre- and
postdiagnosis physical activity on mortality in breast cancer survivors: The health,
eating, activity, and lifestyle study. J Clin Oncol 26(24):3958-3964.
Irwin, M. L., K. Varma, M. Alvarez-Reeves, L. Cadmus, A. Wiley, G. G. Chung, L. Dipietro,
S. T. Mayne, and H. Yu. 2009. Randomized controlled trial of aerobic exercise on
insulin and insulin-like growth factors in breast cancer survivors: The Yale Exercise and
Survivorship study. Cancer Epidemiol Biomarkers Prev 18(1):306-313.
Irwin, M. L., C. Duggan, C. Y. Wang, A. W. Smith, A. McTiernan, R. N. Baumgartner, K. B.
Baumgartner, L. Bernstein, and R. Ballard-Barbash. 2011. Fasting C-peptide levels
and death resulting from all causes and breast cancer: The health, eating, activity, and
lifestyle study. J Clin Oncol 29(1):47-53.
OCR for page 76
76 THE ROLE OF OBESITY IN CANCER
Jakicic, J. M., C. Winters, W. Lang, and R. R. Wing. 1999. Effects of intermittent exercise
and use of home exercise equipment on adherence, weight loss, and fitness in overweight
women: A randomized trial. JAMA 282(16):1554-1560.
Jebb, S. A., A. L. Ahern, A. D. Olson, L. M. Aston, C. Holzapfel, J. Stoll, U. Amann-Gassner,
A. E. Simpson, N. R. Fuller, S. Pearson, N. S. Lau, A. P. Mander, H. Hauner, and I. D.
Caterson. 2011. Primary care referral to a commercial provider for weight loss treatment
versus standard care: A randomised controlled trial. Lancet 378(9801):1485-1492.
Jiralerspong, S., S. L. Palla, S. H. Giordano, F. Meric-Bernstam, C. Liedtke, C. M. Barnett, L.
Hsu, M. C. Hung, G. N. Hortobagyi, and A. M. Gonzalez-Angulo. 2009. Metformin
and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients
with breast cancer. J Clin Oncol 27(20):3297-3302.
Joshu, C. E., A. M. Mondul, A. Menke, C. Meinhold, M. Han, E. B. Humphreys,
S. J. Freedland, P. C. Walsh, and E. A. Platz. 2011. Weight gain is associated with an
increased risk of prostate cancer recurrence after prostatectomy in the PSA era. Cancer
Prev Res (Phila) 4(4):544-551.
Kakarala, M., and M. S. Wicha. 2008. Implications of the cancer stem-cell hypothesis for
breast cancer prevention and therapy. J Clin Oncol 26(17):2813-2820.
Kakarala, M., D. E. Brenner, H. Korkaya, C. Cheng, K. Tazi, C. Ginestier, S. Liu, G.
Dontu, and M. S. Wicha. 2010a. Targeting breast stem cells with the cancer preventive
compounds curcumin and piperine. Breast Cancer Res Treat 122(3):777-785.
Kakarala, M., S. K. Dubey, M. Tarnowski, C. Cheng, S. Liyanage, T. Strawder, K. Tazi, A.
Sen, Z. Djuric, and D. E. Brenner. 2010b. Ultra-low flow liquid chromatography assay
with ultraviolet (UV) detection for piperine quantitation in human plasma. J Agric Food
Chem 58(11):6594-6599.
Knowler, W. C., E. Barrett-Connor, S. E. Fowler, R. F. Hamman, J. M. Lachin, E. A. Walker,
and D. M. Nathan. 2002. Reduction in the incidence of type 2 diabetes with lifestyle
intervention or metformin. N Engl J Med 346(6):393-403.
Knox, L. S., L. O. Crosby, I. D. Feurer, G. P. Buzby, C. L. Miller, and J. L. Mullen. 1983.
Energy expenditure in malnourished cancer patients. Ann Surg 197(2):152-162.
Kroenke, C. H., W. Y. Chen, B. Rosner, and M. D. Holmes. 2005. Weight, weight gain, and
survival after breast cancer diagnosis. J Clin Oncol 23(7):1370-1378.
Leblanc, E. S., E. O’Connor, E. P. Whitlock, C. D. Patnode, and T. Kapka. 2011. Effectiveness
of primary care-relevant treatments for obesity in adults: A systematic evidence review
for the U.S. Preventive Services Task Force. Ann Intern Med 155(7):434-447.
LeRoith, D. 2010. Can endogenous hyperinsulinaemia explain the increased risk of cancer
development and mortality in type 2 diabetes: Evidence from mouse models. Diabetes
Metab Res Rev 26(8):599-601.
Libby, G., L. A. Donnelly, P. T. Donnan, D. R. Alessi, A. D. Morris, and J. M. Evans. 2009.
New users of metformin are at low risk of incident cancer: A cohort study among people
with type 2 diabetes. Diabetes Care 32(9):1620-1625.
Ligibel, J. 2011. Obesity and breast cancer. Oncology 25(11):994-1000.
Ligibel, J. A., N. Campbell, A. Partridge, W. Y. Chen, T. Salinardi, H. Chen, K. Adloff, A.
Keshaviah, and E. P. Winer. 2008. Impact of a mixed strength and endurance exercise
intervention on insulin levels in breast cancer survivors. J Clin Oncol 26(6):907-912.
OCR for page 77
77
WORKSHOP SUMMARY
Ma, J., H. Li, E. Giovannucci, L. Mucci, W. Qiu, P. L. Nguyen, J. M. Gaziano, M. Pollak, and
M. J. Stampfer. 2008. Prediagnostic body-mass index, plasma C-peptide concentration,
and prostate cancer-specific mortality in men with prostate cancer: A long-term survival
analysis. Lancet Oncol 9(11):1039-1047.
Macedo, L. F., G. J. Sabnis, O. G. Goloubeva, and A. Brodie. 2008. Combination of
anastrozole with fulvestrant in the intratumoral aromatase xenograft model. Cancer Res
68(9):3516-3522.
Mai, V., L. H. Colbert, D. Berrigan, S. N. Perkins, R. Pfeiffer, J. A. Lavigne, E. Lanza,
D. C. Haines, A. Schatzkin, and S. D. Hursting. 2003. Calorie restriction and diet
composition modulate spontaneous intestinal tumorigenesis in Apc(Min) mice through
different mechanisms. Cancer Res 63(8):1752-1755.
Mancino, L., and J. Guthrie. 2009. When nudging in the lunch line might be a good thing.
Amber Waves 7(1):32-38.
Mason, C., K. E. Foster-Schubert, I. Imayama, A. Kong, L. Xiao, C. Bain, K. L. Campbell,
C. Y. Wang, C. R. Duggan, C. M. Ulrich, C. M. Alfano, G. L. Blackburn, and A.
McTiernan. 2011. Dietary weight loss and exercise effects on insulin resistance in
postmenopausal women. Am J Prev Med 41(4):366-375.
Menendez, J. A., S. Cufi, C. Oliveras-Ferraros, B. Martin-Castillo, J. Joven, L. Vellon, and
A. Vazquez-Martin. 2011. Metformin and the ATM DNA damage response (DDR):
Accelerating the onset of stress-induced senescence to boost protection against cancer.
Aging 3(11):1063-1077.
Meyerhardt, J. A., D. Heseltine, D. Niedzwiecki, D. Hollis, L. B. Saltz, R. J. Mayer, J.
Thomas, H. Nelson, R. Whittom, A. Hantel, R. L. Schilsky, and C. S. Fuchs. 2006.
Impact of physical activity on cancer recurrence and survival in patients with stage III
colon cancer: Findings from CALGB 89803. J Clin Oncol 24(22):3535-3541.
Meyerhardt, J. A., D. Niedzwiecki, D. Hollis, L. B. Saltz, F. B. Hu, R. J. Mayer, H. Nelson,
R. Whittom, A. Hantel, J. Thomas, and C. S. Fuchs. 2007. Association of dietary
patterns with cancer recurrence and survival in patients with stage III colon cancer.
JAMA 298(7):754-764.
Meyerhardt, J. A., J. Ma, and K. S. Courneya. 2010. Energetics in colorectal and prostate
cancer. J Clin Oncol 28(26):4066-4073.
Moore, T., L. Beltran, S. Carbajal, S. Strom, J. Traag, S. D. Hursting, and J. DiGiovanni.
2008a. Dietary energy balance modulates signaling through the Akt/mammalian target
of rapamycin pathways in multiple epithelial tissues. Cancer Prev Res (Phila) 1(1):65-76.
Moore, T., S. Carbajal, L. Beltran, S. N. Perkins, S. Yakar, D. Leroith, S. D. Hursting, and
J. DiGiovanni. 2008b. Reduced susceptibility to two-stage skin carcinogenesis in mice
with low circulating insulin-like growth factor I levels. Cancer Res 68(10):3680-3688.
NIH (National Institutes of Health). 2000. The practical guide: Identification, evaluation,
and treatment of overweight and obesity in adults. http://www.nhlbi.nih.gov/guidelines/
obesity/prctgd_c.pdf (accessed January 10, 2012).
Nock, N. L., and N. A. Berger. 2010. Obesity and cancer: Overview of mechanism, in cancer
and energy balance, epidemiology and overview. Edited by N. A. Berger. New York:
Springer.
OCR for page 78
78 THE ROLE OF OBESITY IN CANCER
Padovani, M., J. A. Lavigne, G. V. Chandramouli, S. N. Perkins, J. C. Barrett, S. D. Hursting,
L. M. Bennett, and D. Berrigan. 2009. Distinct effects of calorie restriction and
exercise on mammary gland gene expression in C57BL/6 mice. Cancer Prev Res (Phila)
2(12):1076-1087.
Perri, M. G., D. A. McAllister, J. J. Gange, R. C. Jordan, G. McAdoo, and A. M. Nezu.
1988. Effects of four maintenance programs on the long-term management of obesity.
J Consult Clin Psychol 56(4):529-534.
Pi-Sunyer, F. X. 2000. Overnutrition and undernutrition as modifiers of metabolic processes
in disease states. Am J Clin Nutr 72(2 Suppl):533S-537S.
Pi-Sunyer, X., G. Blackburn, F. L. Brancati, G. A. Bray, R. Bright, J. M. Clark, J. M. Curtis,
M. A. Espeland, J. P. Foreyt, K. Graves, S. M. Haffner, B. Harrison, J. O. Hill, E. S.
Horton, J. Jakicic, R. W. Jeffery, K. C. Johnson, S. Kahn, D. E. Kelley, A. E. Kitabchi,
W. C. Knowler, C. E. Lewis, B. J. Maschak-Carey, B. Montgomery, D. M. Nathan,
J. Patricio, A. Peters, J. B. Redmon, R. S. Reeves, D. H. Ryan, M. Safford, B. Van
Dorsten, T. A. Wadden, L. Wagenknecht, J. Wesche-Thobaben, R. R. Wing, and
S. Z. Yanovski. 2007. Reduction in weight and cardiovascular disease risk factors in
individuals with type 2 diabetes: One-year results of the look AHEAD trial. Diabetes
Care 30(6):1374-1383.
Pierce, J. P., L. Natarajan, B. J. Caan, B. A. Parker, E. R. Greenberg, S. W. Flatt, C. L. Rock,
S. Kealey, W. K. Al-Delaimy, W. A. Bardwell, R. W. Carlson, J. A. Emond, S. Faerber,
E. B. Gold, R. A. Hajek, K. Hollenbach, L. A. Jones, N. Karanja, L. Madlensky, J.
Marshall, V. A. Newman, C. Ritenbaugh, C. A. Thomson, L. Wasserman, and M. L.
Stefanick. 2007a. Influence of a diet very high in vegetables, fruit, and fiber and low in
fat on prognosis following treatment for breast cancer: The Women’s Healthy Eating
and Living (WHEL) randomized trial. JAMA 298(3):289-298.
Pierce, J. P., M. L. Stefanick, S. W. Flatt, L. Natarajan, B. Sternfeld, L. Madlensky, W. K.
Al-Delaimy, C. A. Thomson, S. Kealey, R. Hajek, B. A. Parker, V. A. Newman, B. Caan,
and C. L. Rock. 2007b. Greater survival after breast cancer in physically active women
with high vegetable-fruit intake regardless of obesity. J Clin Oncol 25(17):2345-2351.
Pierce, B. L., M. L. Neuhouser, M. H. Wener, L. Bernstein, R. N. Baumgartner, R.
Ballard-Barbash, F. D. Gilliland, K. B. Baumgartner, B. Sorensen, A. McTiernan, and
C. M. Ulrich. 2009. Correlates of circulating C-reactive protein and serum amyloid
A concentrations in breast cancer survivors. Breast Cancer Res Treat 114(1):155-167.
Protani, M., M. Coory, and J. H. Martin. 2010. Effect of obesity on survival of women with
breast cancer: Systematic review and meta-analysis. Breast Cancer Res Treat 123(3):
627-635.
Ranucci, M., S. Castelvecchio, M. Conte, G. Megliola, G. Speziale, F. Fiore, F. Guarracino, S.
Scolletta, R. M. Escobar, M. Falco, E. Bignami, and G. Landoni. 2011. The easier, the
better: Age, creatinine, ejection fraction score for operative mortality risk stratification
in a series of 29,659 patients undergoing elective cardiac surgery. J Thorac Cardiovasc
Surg 142(3):581-586.
Reeves, G. K., K. Pirie, V. Beral, J. Green, E. Spencer, and D. Bull. 2007. Cancer incidence
and mortality in relation to body mass index in the Million Women Study: Cohort
study. BMJ 335(7630):1134.
OCR for page 79
79
WORKSHOP SUMMARY
Rock, C. L., S. W. Flatt, N. E. Sherwood, N. Karanja, B. Pakiz, and C. A. Thomson. 2010.
Effect of a free prepared meal and incentivized weight loss program on weight loss and
weight loss maintenance in obese and overweight women: A randomized controlled
trial. JAMA 304(16):1803-1810.
Rose, D. P., M. Goldman, J. M. Connolly, and L. E. Strong. 1991. High-fiber diet reduces
serum estrogen concentrations in premenopausal women. Am J Clin Nutr 54(3):
520-525.
Sabnis, G., A. Schayowitz, O. Goloubeva, L. Macedo, and A. Brodie. 2009. Trastuzumab
reverses letrozole resistance and amplifies the sensitivity of breast cancer cells to estrogen.
Cancer Res 69(4):1416-1428.
Sacks, F. M., G. A. Bray, V. J. Carey, S. R. Smith, D. H. Ryan, S. D. Anton, K. McManus,
C. M. Champagne, L. M. Bishop, N. Laranjo, M. S. Leboff, J. C. Rood, L. de Jonge,
F. L. Greenway, C. M. Loria, E. Obarzanek, and D. A. Williamson. 2009. Comparison
of weight-loss diets with different compositions of fat, protein, and carbohydrates.
N Engl J Med 360(9):859-873.
Saltz, L. B., D. Niedzwiecki, D. Hollis, R. M. Goldberg, A. Hantel, J. P. Thomas, A. L.
Fields, and R. J. Mayer. 2007. Irinotecan fluorouracil plus leucovorin is not superior
to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer:
Results of CALGB 89803. J Clin Oncol 25(23):3456-3461.
Shoba, G., D. Joy, T. Joseph, M. Majeed, R. Rajendran, and P. S. Srinivas. 1998. Influence
of piperine on the pharmacokinetics of curcumin in animals and human volunteers.
Planta Med 64(4):353-356.
Sjostrom, L., K. Narbro, C. D. Sjostrom, K. Karason, B. Larsson, H. Wedel, T. Lystig, M.
Sullivan, C. Bouchard, B. Carlsson, C. Bengtsson, S. Dahlgren, A. Gummesson, P.
Jacobson, J. Karlsson, A. K. Lindroos, H. Lonroth, I. Naslund, T. Olbers, K. Stenlof, J.
Torgerson, G. Agren, and L. M. Carlsson. 2007. Effects of bariatric surgery on mortality
in Swedish obese subjects. N Engl J Med 357(8):741-752.
Speck, R. M., K. S. Courneya, L. C. Masse, S. Duval, and K. H. Schmitz. 2010. An update
of controlled physical activity trials in cancer survivors: A systematic review and meta-
analysis. J Cancer Surviv 4(2):87-100.
Subbaramaiah, K., L. R. Howe, P. Bhardwaj, B. Du, C. Gravaghi, R. K. Yantiss, X. K. Zhou,
V. A. Blaho, T. Hla, P. Yang, L. Kopelovich, C. A. Hudis, and A. J. Dannenberg. 2011.
Obesity is associated with inflammation and elevated aromatase expression in the mouse
mammary gland. Cancer Prev Res (Phila) 4(3):329-346.
Thompson, E. W., and I. Haviv. 2011. The social aspects of EMT-MET plasticity. Nature
Medicine 17(9):1048-1049.
TREC (Transdisciplinary Research on Energetics and Cancer). 2012. TREC overview. http://
www.trecscience.org/trec/bin/about/overview.aspx?j=21 (accessed January 10, 2012).
USPSTF (U.S. Preventive Services Task Force). 2003. Screening for obesity in adults:
Recommendations and rationale. Ann Intern Med 139(11):930-932.
Wadden, T. A, R. H. Neiberg, R. R. Wing, J. M. Clark, L. M. Delahanty, J. O. Hill, J.
Krakoff, A. Otto, D. H. Ryan, M. Z. Vitolins; Look AHEAD Research Group. 2011.
Four-year weight losses in the Look AHEAD study: Factors associated with long-term
success. Obesity 19(10):1987-1998.
Wisse, B. E., F. Kim, and M. W. Schwartz. 2007. An integrative view of obesity. Science
318(5852):928-929.
OCR for page 80
80 THE ROLE OF OBESITY IN CANCER
Wolpin, B. M., J. A. Meyerhardt, A. T. Chan, K. Ng, J. A. Chan, K. Wu, M. N. Pollak, E. L.
Giovannucci, and C. S. Fuchs. 2009. Insulin, the insulin-like growth factor axis, and
mortality in patients with nonmetastatic colorectal cancer. J Clin Oncol 27(2):176-185.
World Cancer Reasearch Fund and American Institute for Cancer Research. 2007. Food,
nutrition, physical activity, and the prevention of cancer: A global perspective. http://www.
dietandcancerreport.org/cancer_resource_center/downloads/summary/english.pdf
(accessed January 9, 2012).
Wright, M. E., S. C. Chang, A. Schatzkin, D. Albanes, V. Kipnis, T. Mouw, P. Hurwitz, A.
Hollenbeck, and M. F. Leitzmann. 2007. Prospective study of adiposity and weight
change in relation to prostate cancer incidence and mortality. Cancer 109(4):675-684.
Zheng, Q., S. M. Dunlap, J. Zhu, E. Downs-Kelly, J. Rich, S. D. Hursting, N. A. Berger,
and O. Reizes. 2011. Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor
growth in obese mice and abrogates tumor initiating cell survival. Endocr Relat Cancer
18(4):491-503.
