Obesity and Cancer Risk

Program on Breast Cancer
Environmental Risk Factors
Fa c t S h e e t # 5 7 • N o v e m b e r 2 0 0 7
TOPICS
Obesity and Cancer Risk
Cancers associated
Summary
with obesity
Obesity has been associated with increased risk of a number
Cancers likely to
of types of cancer. The risk of cancers of the colon and
be associated with
rectum, breast, body of the uterus (endometrium), kidney
obesity
and esophagus have all been associated with obesity. Other
Cancers with
insufficient evidence
cancers whose risk is likely to be related to obesity are
for a relationship
cancers of the pancreas, liver, gall bladder and the cardia
with obesity
(uppermost region) of the stomach. The level of risk for
Cancers unlikely to
most of these cancers is moderate, having relative risk
be related to obesity
values between 1.5 and 2.9. The contribution of obesity to
The impact of
the occurrence of cancer is considerable. In high income
obesity on cancer
countries, such as the United States, obesity is considered to
How obesity might
be the third largest contributor to cancer incidence behind
lead to cancer
smoking and alcohol use.
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and Environmental Risk
Factors (BCERF)
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necessarily reflect the views of these agencies.

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Obesity and Cancer Risk
Fact Sheet #57 • November 2007
What types of cancer are
associated with obesity?
Table1 Relative Risk Values of Cancers
ASSOCIATED with Obesity
Relative Risk Range
Introduction and Overview
Type of Cancer
(Level of Risk)
The association between obesity and different types of
cancer are described in the sections below. In this
Colon and Rectum, Men
1.5 – 2.0 (Moderate)
discussion, cancers are divided into four groups, based
Colon and Rectum, Women
1.2 – 1.5 (Weak)
on the strength of the scientific evidence relating them
Postmenopausal Breast
1.5 – 2.5 (Moderate)
to obesity. The four groups are: a) cancers associated
Endometrium
2.0 – 3.5
with obesity; b) cancers likely to be associated with
(Body of the Uterus)
(Moderate to Strong)
obesity; c) cancers for which there is insufficient
Kidney
2.0 (Moderate)
evidence of an association with obesity; and d) cancers
Esophagus
2.0 – 3.0 (Moderate)
unlikely to be associated with obesity. There are two
summary tables. Table 1 summarizes the strength of the
obesity-related relative risk for the cancers associated
A) Obesity and Risk of Cancer of the Colon
with obesity. Table 2 summarizes the same information
and Rectum
for cancers that are likely to be associated with obesity.
Incidence of Cancer of the Colon and Rectum
It is also important to note that most studies of
Cancer of the colon and rectum is the third most
obesity use a measure called body mass index (BMI). BMI
common cancer in both men and women. It is
is calculated by dividing weight in kilograms by height in
estimated that there will be 112,340 new cases of colon
meters squared (kg/m2). This calculation compensates for
cancer and 41,420 new cases of rectal cancer
differences in body size between people and while it is
diagnosed in 2007. An estimated 52,180 deaths will
not a direct measure of body fat, it is used as a gross
occur from colorectal cancer in 2007; this is 10% of all
indicator of body fat. The World Health Organization
cancer deaths for men and 11% for women. The
defines overweight as a BMI of 25 or greater and obesity
incidence of these cancers has decreased over the last
as a BMI of 30 or greater. The National Heart, Lung and
20 years probably due at least in part to screening
Blood Institute has a BMI calculator at their web site
(colonoscopy) and early cancer (polyp) removal.
(http://www.nhlbisupport.com/bmi/).
These studies also use a measure of cancer risk
Effect of Obesity on the Risk of Cancer of the
called the relative risk. In the context of this discussion,
Colon and Rectum
relative risk would be the chance of obese people
An increase in the risk of colon and rectal cancer has been
getting a certain type of cancer compared to the
consistently associated with obesity. The obesity-related
chance of normal weight people getting this type of
cancer risk has been found to be higher in men than in
cancer. For a more through discussion of cancer risk
women. Obese men have a moderately increased risk of
please see BCERF Fact Sheet # 49, Understanding Breast
1.5 to 2 times the risk of colon and rectal cancer
Cancer Risk and Risk Factors Associated with Diet and
compared to non-obese men. In women, obesity-related
Lifestyle.
relative risk typically ranges from 1.2 to 1.5. Similar
results have been reported for the association of obesity
1. Cancers Associated with Obesity
with the risk of early non-malignant colon tumors called
There is sufficient evidence, for cancers within this
adenomas. Waist-to-hip ratio, a measure of how fat is
group, to be assigned an association of increased risk
carried or body fat distribution also has a similar risk
with obesity. Cancers of the colon and rectum, breast,
association. The reason for the difference in obesity-
endometrium, kidney and esophagus make up this
related risk between men and women is uncertain, but it
group. Each type of cancer is described separately
may be at least partially explained by the inhibition of
below. Table 1 summarizes the risk levels and values
colon and rectum cancer growth by estrogen. The IARC
reported for cancers associated with obesity.
(International Agency for Research on Cancer) working
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Fact Sheet #57 • November 2007
Obesity and Cancer Risk
group on cancer prevention has concluded that there is
an increase in endometrial cancer risk. Obese women
enough evidence to recommend prevention of weight
are 2 to 3.5 times more likely to develop endometrial
gain to reduce the risk of colon and rectal cancer.
cancer than non-obese women. This is considered a
moderate to strong association. Most studies have seen
B) Obesity and Risk of Cancer of the Breast
a gradual increase in the risk of getting endometrial
Incidence
cancer along with increases in BMI. This indicates that
The American Cancer Society has estimated that there
normal weight women have lower risk of getting
will be 180,510 cases of invasive breast cancer
endometrial cancer, overweight women have higher
diagnosed in 2007. Of this total, 2,030 (1.1%) will be
risk, and obese women have the highest level of risk.
diagnosed in men. Breast cancer is the most commonly
Some studies have examined premenopausal and post-
diagnosed cancer in women. There will be an estimated
menopausal women separately. Most, but not all, of
40,910 breast cancer deaths in 2007. Breast cancer is,
these studies found increased risk of endometrial cancer
after lung cancer, the second largest source of cancer
among obese women in both age groups but with
death for women. Fifteen percent of all deaths from
greater risk for older obese women.
cancer in women are due to cancer of the breast.
D) Obesity and Risk of Cancer of the Kidney
Effect of Obesity on the Risk of Cancer of the Breast
Incidence
Obesity is a well established risk factor for
Kidney cancer makes up about 3.5% of all new cancers
postmenopausal breast cancer.
Postmenopausal
in the U.S. This is equal to 51,190 cases diagnosed in
women whose BMI falls in the obese category have
2007. These cases are generally of two types, renal cell
about twice the breast cancer risk of women with a BMI
cancer and cancer of the renal pelvis. Approximately
in the normal weight category. The association between
85% of all kidney cancers are renal cell cancers, and this
obesity and breast cancer is complex as reflected by the
is the type of renal cancer that is associated with obesi-
fact that the relationship with premenopausal breast
ty. The incidence of renal cancer in men is about twice
cancer is the opposite of that seen postmenopausally.
that in women. There are estimated to be 12,890
Obesity in postmenopausal women is associated with a
deaths from renal cancer in the U.S. in 2007.
moderate increase in breast cancer risk but obesity in
premenopausal women is associated with a weak
Effect of Obesity on the Risk of Cancer of the Kidney
decrease in breast cancer risk. Obesity has also been
Almost all studies of the association of obesity and renal
well demonstrated to have negative effects on breast
cell cancer have found that obesity is associated with
cancer diagnosis and survival. The relationship of
more than a doubling of relative risk. These results are fur-
obesity and breast cancer risk is discussed in more detail
ther strengthened by the consistency of results from stud-
in BCERF Fact Sheet #56, Obesity and Breast Cancer Risk.
ies conducted in a number of countries. Investigations
have also reported similar dose response relationships
C) Obesity and Risk of Cancer of the
between BMI and renal cell cancer; this indicates that
Endometrium (Body of the Uterus)
heavier people have greater risk than lighter people. Some
Incidence
studies have reported a larger level of risk for women than
It is estimated that 39,080 cases of endometrial cancer
men but these results need further study.
will be diagnosed in 2007. This makes it the fourth most
common cancer in women. 7,400 women are predict-
E) Obesity and Risk of Cancer of the Esophagus
ed to die from this cancer in 2007. Endometrial cancer
Incidence
accounts for 3% of all cancer deaths.
The incidence of cancer of the esophagus varies greatly
throughout the world. It is uncommon in the U.S. but its
Effect of Obesity on the Risk of Cancer of the
prevalence is growing at a rapid rate in this and all
Endometrium
developed countries. Studies of esophageal cancer in the
There is convincing evidence from both case-control
U.S. have recently reported a 21% increase in the
and cohort studies that adult obesity is associated with
incidence of adenocarcinoma of the esophagus. In
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Obesity and Cancer Risk
Fact Sheet #57 • November 2007
contrast, the incidence of a second type of esophageal
cancer, squamous-cell cancer, has remained stable.
Table2 Relative Risk Values of
15,560 new cases of cancer of the esophagus are
Cancers LIKELY TO BE
predicted for 2007; this is not a very common cancer, as
Associated with Obesity
its incidence is 1% of all cancer cases. It is estimated that
Relative Risk Range
there will be 13,940 deaths in 2007 from this disease.
Type of Cancer
(Level of Risk)
Effect of Obesity on the Risk of Cancer
Pancreas
2.0 (Moderate)
of the Esophagus
Liver
1.5 – 4.0
Obesity has been linked to a 2 to 3 fold increase in the
(Moderate to Strong)
risk of adenocarcinoma occurring in the lower third of
Gall Bladder
2.0 (Moderate)
the esophagus, but it is unrelated to the risk of
Gastric Cardia
1.5 – 2.0 (Moderate)
squamous-cell cancer of the esophagus. The increased
risk of esophageal cancer associated with obesity is
Non-Hodgkin Lymphoma
1.4 – 2.0 (Moderate)
thought, by many investigators, to be linked to the
effects of gastro-esophageal reflux disease (GERD).
cancer for both men and women. In 2007, there are pre-
In healthy people, the highly acidic contents of the
dicted to be 33,370 deaths from cancer of the pancreas.
stomach are separated from the esophagus by a valve-
like closure known as the lower esophageal sphincter.
Effect of Obesity on the Risk of Cancer
However, for people with GERD, the sphincter does not
of the Pancreas
close well and allows some of the stomach’s contents to
A number of recent studies have reported a doubling of
reach and damage the esophagus. GERD can be linked to
the risk of cancer of the pancreas related to obesity.
obesity but the nature of this linkage is uncertain.
However, earlier, and smaller studies, have reported low
Possible explanations include effects of fat-related
risk and in some cases no association of obesity with
hormones and increases in stomach pressure resulting
pancreatic cancer risk. More study will be needed to
from larger amounts of abdominal fat tissue. Even
sort out these different findings. However, there is a
though the association of obesity and adenocarcinoma is
strong potential mechanism for a link between obesity
well established, the role of GERD in the cancer formation
and pancreatic cancer provided by diabetes. The risk of
is still uncertain. Two studies have not supported the
diabetes has been very strongly linked to obesity, and
relationship of GERD and esophageal cancer.
diabetes has a well established association with pancre-
atic cancer risk. Thus, obesity may be indirectly related
2. Cancers Likely to be Associated with
to an increase in the risk of cancer of the pancreas by its
Obesity
very strong association with diabetes.
For cancers within this group there is insufficient
evidence to indicate a definite association of their risk
B) Obesity and Risk of Cancer of the Liver
with obesity. However, there is sufficient evidence to
Incidence
indicate that, in all likelihood, their risk is associated
In 2007, it is predicted that there will be 19,160 new
with obesity. These cancers include cancer of the
cases of cancer of the liver and bile duct. This is an
pancreas, liver, gall bladder, and gastric cardia. Each is
uncommon cancer and its number of new cases is just
described below. Table 2 summarizes the risk levels and
over one percent of the predicted total number of new
values reported for these cancers.
cancer cases, in general. 16,780 people are expected to
die of this disease in 2007.
A) Obesity and Risk of Cancer of the Pancreas
Incidence
Effect of Obesity on the Risk of Cancer of the Liver
The estimated number of new cases of cancer of the
Only five studies have examined the association
pancreas in the U.S., in 2007, is 37,170. This is not a
between obesity and liver cancer. Four of these studies
common cancer as it makes up 2.6% of all new cases of
reported an increased risk of liver cancer but with
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Fact Sheet #57 • November 2007
Obesity and Cancer Risk
widely ranging levels of risk. The fifth study, in contrast,
these studies have reported a higher risk for women but
found no association. These results suggest that it is
more study will be required to resolve this concern.
likely that liver cancer is associated with obesity, but
more research will be needed to fully resolve this issue.
3. Other Cancers for Which There is
There have only been seven studies that evaluated
Insufficient Evidence for an
the relationship between obesity and gall bladder
Association with Obesity
cancer. Although these studies have been small, they
Studies of varying numbers and sizes have examined the
have consistently reported a doubling of risk of gall
relationship between obesity and the risk of: testicular
bladder cancer among obese individuals.
cancer, thyroid cancer, cervical cancer, malignant
melanoma, and cancers of the head and neck. There is
C) Obesity and Risk of Cancer of the Gastric
currently insufficient evidence for any judgments to be
Cardia (Uppermost Region of the Stomach)
made about the relationship of these cancers to obesity.
Incidence
In 2007, an estimated 21,260 people (13,000 men and
4. Cancers Which are Unlikely to be
8,260 women) are predicted to be diagnosed with
Associated with Obesity
stomach cancer. The number of deaths from stomach
Cancers within this group have received sufficient study
cancer in 2007 is estimated to be 11,210 with almost
to determine that their risk has no association with obe-
60% of these deaths in men and the rest in women.
sity. They include lung cancer, ovarian cancer, and
While cancer occurs in other parts of the stomach,
prostate cancer.
currently about half of all stomach cancers in the U.S.
Lung Cancer. Smoking is the main cause of lung
are in the gastric cardia region.
cancer and can affect body weight. Accordingly, the
clearest way to examine a potential an association
Effect of Obesity on the Risk of Cancer
between obesity and lung cancer is among groups of
of the Gastric Cardia
non-smokers. Three studies of nonsmokers have exam-
A number of studies have reported an increase in the
ined this relationship. The two larger studies found no
risk of cancer of the gastric cardia linked to obesity with
association between obesity and lung cancer while the
weak to moderate levels of risk.
smaller study found that obesity was associated with
decreased risk.
D) Obesity and Risk of Non-Hodgkin
Ovarian Cancer. Most studies examining obesity
Lymphoma
and ovarian cancer risk have reported the lack of a risk
Incidence
association. An association would not be surprising.
In 2007, the number of new cases of non-Hodgkin lym-
Ovarian cancer is considered a hormone related cancer
phoma is forecasted to reach 63,190 (34,200 in men
and obesity can affect hormone levels. Nonetheless,
and 28,990 in women). During this year, the number of
existing studies indicate that there is no relationship
deaths from non-Hodgkin lymphoma is estimated to be
between obesity and the risk of ovarian cancer.
18,660; this accounts for 3% of all cancer deaths in
Prostate Cancer. Three recent, large studies of
men and women. The incidence of this disease in the
obesity and prostate cancer have reported a weak
U.S. has been stable for the past 5 years. This follows a
(relative risk values of 1.09 to 1.27) but statistically
period beginning in the early 70’s which saw an unex-
supported (or significant) association. However, there
plained near doubling of its incidence rate.
are a large number of earlier studies that found no
association between obesity and prostate cancer risk. In
Effect of Obesity on the Risk of
further support of a lack of an association, the earlier
Non-Hodgkin Lymphoma
studies were carried out in a number of different
Sixteen case-control and cohort studies have examined
countries, and evaluated a number of different aspects
the association of non-Hodgkin lymphoma and obesity.
of this association. The IARC working group has
They have generally shown a moderate increase in the
concluded that it is unlikely that any important
risk of this form of cancer related to obesity. A few of
association between obesity and prostate cancer exists.
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Obesity and Cancer Risk
Fact Sheet #57 • November 2007
Recent studies have examined aggressive and non-
eliminated 57% of all the cases of endometrial cancer in
aggressive prostate cancers separately. These studies
the population would also be theoretically eliminated.
have raised the possibility that obesity may increase the
The results in this table are dramatic. For the cancers
risk of aggressive prostate cancer yet decrease the risk
which have been shown to be associated with obesity,
of the non-aggressive form of this disease. More study
the elimination of obesity would eliminate from one fifth
will be required to resolve this issue.
to almost two thirds of these types of cancer. This is a
considerable fraction of cases of these cancers within the
population and indicates the large impact obesity has on
Is there a way to estimate
these cancers.
the impact of obesity on the
incidence of different types
How large is the effect of
of cancer?
obesity on death from cancer,
The impact of obesity on the incidence of various types
in general?
of cancers can be estimated using an epidemiological
A recent study of 900,000 U.S. residents examined the
statistic known as population attributable fraction. This
relationship of obesity to the risk of death from cancer.
statistic is calculated from the strength of the risk of
Since smoking is such a large contributor to cancer, the
each cancer’s association with obesity and from how
most relevant analyses examined nonsmokers only
common obesity is in the population. The result is
(383,594 participants). Among nonsmokers, the most
presented as a percentage. The population attributable
obese women had a relative risk of death from cancer
fraction for obesity and different cancers is most easily
which was 1.9 times that of the normal weight women.
understood as the percentage of all the cases of each
The comparable value for men was 1.3.
type of cancer that would theoretically be eliminated if
The population attributable fraction for obesity and
obesity was eliminated. An example can be made using
cancer death was also determined. The percentage of
the population attributable fraction value for
nonsmoking women’s cancer deaths that were
endometrial cancer in Table 3. Its value is 57% and this
attributed to obesity was 20% and the value for men
indicates that if all obesity in the U.S. population was
was 14%. As these values demonstrate, obesity has a
considerable impact on death from all forms of cancer.
Table 3 Population Attributable
Fraction Values for
How is obesity thought to
Cancers Associated With Obesity
biologically influence the
Population
Type of Cancer
Attributable
formation of cancer?
Fraction
How obesity might affect cancer risk is not clearly
Colon and Rectum, Men
35%
understood. Several interrelated explanations have been
presented. Some of these explanations are discussed
Colon and Rectum, Women
21%
below.
Breast
23%
Fat cells have been shown to produce substances
Endometrium
57%
that may increase cancer risk. A number of hormone-
(Body of the Uterus)
like substances are produced by fat cells. Some of these
hormone-line substances have effects on the growth of
Kidney
43%
cancer cells in the laboratory, and increases in these
Esophagus
52%
hormones could potentially increase cancer risk.
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Fact Sheet #57 • November 2007
Obesity and Cancer Risk
Obesity leads to other hormonal changes that can
Obesity has also been linked to the promotion
affect cancer risk. The two most studied hormonal
of what has been called a low grade of chronic
pathways are the insulin-related pathways and the
inflammation. This condition results in the formation of a
estrogen related pathways. Obesity can have effects on
number of cellular signaling agents (cytokines) which are
the levels of insulin in the body and of levels of a related
potentially linked to cancer formation through several
hormone, insulin-like growth factor (IGF). Both insulin
mechanisms including proliferation and genetic damage.
and IGF can increase the growth rate of cancer cells,
and may also have effects on other hormones.
It is well established that the amount of estrogen in
What can people do now?
the body and the length of exposure to estrogen is linked
While sustained weight loss is difficult to achieve,
to postmenopausal breast cancer and endometrial
preventing weight gain provides many health benefits,
cancer risk in women. Studies have reported a direct
including decreased cancer risk. More importantly, it is
relationship between body mass index and estrogen
something that most people can accomplish. Studies
levels after, but not before, menopause. This effect has
have shown that weight gain occurs gradually and
been reported in men as well. The increased estrogen
results from as little as 100 excess Calories a day. This is
exposure is thought to arise from the activity of a key
not a large number of calories, 100 Calories is the
enzyme found in fat cells. This enzyme, aromatase, is able
equivalent of a 15 to 20 minute walk or one pat of
to produce estrogen from other hormones.
butter. But the daily effect of these extra calories builds
There is another way through which obesity may
up over time leading to gradual but definite weight
lead to a larger exposure to estrogen. This is through an
gain. Preventing this daily excess by adding a short walk
obesity-related decrease in the levels of the protein in
or eliminating 100 extra calories from food can have a
the blood that acts as a carrier for estrogen, the sex
substantial effect when done on a daily basis. In
hormone binding globulin. The decrease in this carrier
addition to decreasing cancer risk, other substantial
protein makes estrogen more available in the body and
health benefits can be gained such as decreased risk of
increases its activities, including those that are related
heart disease, diabetes and some forms of arthritis. a
to cancer formation.
Authors:
Barbour S Warren, PhD, Research Associate, BCERF
and
Carol M Devine, Associate Professor, BCERF and the Division of Nutritional Sciences
A complete bibliography of references used in the preparation
of this fact sheet is available on the BCERF web site at
http://envirocancer.cornell.edu
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