Transcript Slide 1

Obesity and Cancer: What can we
learn from weight loss studies?
Faina Linkov, PhD
Research Assistant Professor
University of Pittsburgh Cancer Institute
What is cancer?
Cancer is a term used for
diseases in which abnormal
cells divide without control
and are able to invade other
tissues. Cancer cells can
spread to other parts of the
body through the blood
and lymph systems. Cancer is
not just one disease but many
diseases. There are more than
100 different types of cancer.
(NCI)
(Image from Understanding Cancer Series: Cancer.)
Why is it important to prevent cancer?
• Treatment options are not available for several
forms of cancer
• Existing cancer treatments do not target specific
cancer cells
• Existing cancer treatments have many
undesirable side effects and are not always 100%
effective
• One of the main causes of failure in the
treatment of cancer is the development of drug
resistance by the cancer cells.
Obesity: Smoking gun of cancer
We all know about dangers of
smoking in relation to cancer,
however when it comes to
dangers of obesity in relation to
cancer, there is some state of
confusion.
Why?
Historical data
Obesity Trends* Among U.S. Adults
BRFSS, 2005
(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)
No Data
<10%
10%–14%
15%–19%
20%–24%
25%–29%
≥30%
Obesity and Cancer: Mechanisms
• Adipose tissue is an active endocrine organ
• Mechanisms by which adipose tissue may influence
cancer risk
- Production of sex steroid hormones (e.g., estrogen, androgen)
- Effects on insulin sensitivity and production of insulin-like growth
factors
- Actions on other hormones in adipose tissue (e.g., leptin,
adiponectin)
- Increases in oxidative stress and chronic low-grade inflammation
that affect the body’s immune response
What are the sources of confusion in
the field of obesity and cancer?
• Media
• Lack of understanding as to what level of
overweight/obesity produces undesired health
outcomes
• Lack of interdisciplinary studies between
biologists, exercise epidemiologists, cancer
researchers, biobehavioral researchers, and
obesity experts
• Americans do not view cancer as a preventable
condition
What is media saying about
obesity and cancer?
1998
2003
What is the awareness of obesity
as a risk factor for cancer?
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2009 Cancer Risk Awareness
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2005
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Year
2007
2009
Percentage of Americans Who Rate It Their #1
Health Concern
40%
35%
30%
25%
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15%
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5%
0%
Cancer
Heart Attack
Adult Diabetes
Stroke
Percentage of Americans Who Consider It
“Highly Preventable”
How much excess weight is
too much???
Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied
Cohort of U.S. Adults
NEJM 348:1625(April 2003)
• 900,000 adults
– Prospective study, free of cancer
• Self reported height/body weight in beginning
– 16 year follow up
– ~57,000 cancer deaths
Obesity and Mortality from Cancer
NEJM April 2003
For adults ages 25-59, increased mortality
in underweight and obese categories, but
not overweight category.
Mortality from Cancer According to BMI for U.S. Women in the
Cancer Prevention Study II
Calle, E. et al. N Engl J Med 2003;348:1625-1638
Mortality from Cancer According to BMI for
U.S. Men in the
Cancer Prevention Study II
Effects of bariatric surgery on cancer incidence in obese
patients in Sweden (Swedish Obese Subjects Study):
a prospective, controlled intervention trial
First intervention trial in the obese population to provide
prospective, controlled cancer-incidence data.
The SOS study started in 1987 and involved 2010 obese
patients (body-mass index [BMI] ≥34 kg/m2 in men, and ≥38
kg/m2 in women) who underwent bariatric surgery and 2037
contemporaneously matched obese controls, who received
conventional treatment. While the main endpoint of SOS
was overall mortality, the main outcome of this exploratory
report was cancer incidence until Dec 31, 2005.
My research interests:
Endometrial cancer risk reduction in the context
of weight loss through bariatric surgery
Endometrial Cancer:
Incidence and Prevalence
• Most common gynecologic cancer
• 4th most common in women (US)
• 5th most common in women
(worldwide)
• approximately 39,080 new cases of
endometrial cancer are diagnosed
yearly in the US
• about 7400 women will die from the
disease this year
• Increase in the 1970’s
– Increased use of menopausal estrogen
therapy
Endometrial Carcinoma
Etiology
• Unnoposed estrogen hypothesis:
exposure to unopposed estrogens
(obesity)
Obesity as a risk factor
In comparison with women who maintain a
healthy weight, endometrial cancer is
twice as common in overweight
women, and more than three times as
common in obese women.
Pathology
• Spreads through uterus, fallopian tubes,
ovaries and out into peritoneal cavity
–
Metastasizes via blood and lymphatic
system
Hypothesis
Proposed study theme
• women undergoing bariatric surgery, and its
subsequent weight loss, will have a beneficial
effect on the overall inflammatory and
endocrine status axis and on the QOL as
compared with women who are not losing
weight.
• This effect would ultimately result in stronger
EC prevention.
Why study inflammatory markers?
• Inflammation is an important part of tumor development and
progression
• The knowledge of the levels of inflammatory markers in the
blood of patients is potentially important for early detection
of cancer and monitoring disease progression.
• Lokshin Lab (Luminex Core Facility) has developed a 100marker multiplexed bead-based assay that includes most
known cancer-related soluble proteins in serum.
• Multi-marker panel has superior performance characteristics
as a screening test for ovarian cancer and several other
malignancies.
What kind of studies can we propose?
It is particularly interesting to
explore weight loss in
relation to endometrial
cancer risk because limited
evidence suggests that
premalignant changes in the
endometrium can
potentially be reversed with
achieving more optimal
weight.
Aims
Aim 1
Examine the effects of weight loss surgery on a selected set of biomarkers
associated with the risk of endometrial and other obesity-linked cancers 6,
12, and 24 months following surgery
Aim 2
Investigate the relationships between the magnitude of the weight loss
achieved at 6, 12, and 24 months following surgery and the quantitative
measures of the biomarkers on the obesity-linked cancer risk panel.
Aim 3
To explore the possible additional contribution of changes in physical activity
levels and psychological factors to the changes in quantitative measures of
the biomarkers on the obesity-linked cancer risk panel.
Obesity and Cancer:
Conclusions?
• A healthy diet can help sustain a
healthy weight and lower risk of
cancers
• Regular physical activity protects
against the buildup of excess
body fat and against cancer,
independently
• Bariatric surgery may be used as
a measure of last resort for
people who cannot lose weight
through traditional means