How Might Physical Activity Reduce Cancer Risk

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How Might Physical Activity Reduce Cancer Risk?

• Lisa H. Colbert, PhD, MPH
• Assistant Professor
• Department of Kinesiology
• University of Wisconsin-Madison

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Outline

• the epidemiology of cancer, activity, obesity
• 2. associations between cancer and activity
• possible mechanisms
• A) inflammation
• B) IGF-1 and BPs
• C) body composition
• 4. summary

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2003 Estimated US Cancer Cases
Women658,800
Men675,300
32 Breast 12 Lung bronchus 11 Colon
rectum 6 Uterine corpus 4 Ovary
4 Non-Hodgkin lymphoma 3 Melanoma of
skin 3 Thyroid 2 Pancreas 2 Urinary
bladder 20 All Other Sites
Prostate 33 Lung bronchus 14 Colon
rectum 11 Urinary bladder 6 Melanoma of
skin 4 Non-Hodgkin
lymphoma 4 Kidney 3 Oral Cavity 3 Leukemia 3
Pancreas 2 All Other Sites 17
Excludes basal and squamous cell skin cancers
and in situ carcinomas except urinary
bladder. Source American Cancer Society, 2003.
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2003 Estimated US Cancer Deaths
Men285,900
Women270,600
25 Lung bronchus 15 Breast 11 Colon
rectum 6 Pancreas 5 Ovary 4 Non-Hodgkin
lymphoma 4 Leukemia 3 Uterine
corpus 2 Brain/ONS 2 Multiple
myeloma 23 All other sites
Lung bronchus 31 Prostate 10 Colon
rectum 10 Pancreas 5 Non-Hodgkin 4lymphoma Le
ukemia 4 Esophagus 4 Liver/intrahepatic 3bile
duct Urinary bladder 3 Kidney 3 All other
sites 22
ONSOther nervous system. Excludes basal and
squamous cell skin cancers and in situ carcinomas
except urinary bladder. Source American Cancer
Society, 2003.
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Change in the US Death Rates by Cause, 1950
2000
Rate Per 100,000
1950 2000
Cancer
HeartDiseases
Pneumonia/Influenza
CerebrovascularDiseases
Age-adjusted to the 2000 US standard
population. Source US Mortality Volume 1950,
National Vital Statistics Report, 2002, Vol. 50,
No. 15.
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Trends in Leisure-Time Physical Activity
Prevalence (), Adults 18 and Older, US, 1992-2000
Prevalence ()
Includes fewer than 50 states and the District
of Columbia. All other prevalences include the
50 states and District of Columbia. Source
Behavioral Risk Factor Surveillance System, 1992,
1994, 1996, 1998, 2000, National Center for
Chronic Disease Prevention and Health Promotion,
Centers for Disease Control and Prevention, 1997,
1997, 1999, 2000, 2001.
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Obesity Trends Among U.S. AdultsBRFSS, 1985
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1986
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1987
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
12
Obesity Trends Among U.S. AdultsBRFSS, 1988
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
13
Obesity Trends Among U.S. AdultsBRFSS, 1989
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1990
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1991
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
16
Obesity Trends Among U.S. AdultsBRFSS, 1992
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1993
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1994
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1995
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1996
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1997
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1998
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 1999
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 2000
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Obesity Trends Among U.S. AdultsBRFSS, 2001
Source Mokdad A H, et al. J Am Med Assoc
199928216, 200128610.
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Physical Activity and Colorectal Cancer Risk
Freidenreich, Cancer Epid Biomark Prev,
10287-301, 2001
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Physical Activity and Breast Cancer Risk
Freidenreich, Cancer Epid Biomark Prev,
10287-301, 2001
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Physical Activity and Prostate Cancer Risk
Freidenreich, Cancer Epid Biomark Prev,
10287-301, 2001
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Physical Activity and Endometrial Cancer Risk
Freidenreich, Cancer Epid Biomark Prev,
10287-301, 2001
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Physical Activity and Lung Cancer Risk
Freidenreich, Cancer Epid Biomark Prev,
10287-301, 2001
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Multistage Carcinogenesis
Hursting et al., J Natl Cancer Inst, 1999
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Potential Mechanisms
immunity
transit time bile acid excretion
insulin IGF-1
obesity
Physical Activity Exercise
Cancer
estrogen progesterone testosterone
inflammation
anti-oxidant status
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Integrating the Components of Cancer Prevention
Research
Animal Model Studies
Identify Risk Factors Mechanisms
Basic Molecular/ Cellular Studies
Clinical/Epidemiologic Studies
Effective Human Interventions
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CONCEPTUAL FRAMEWORK FOR ANALYZING POTENTIAL
MECHANISMS
IDEAL
WHAT WE HAVE TO WORK WITH
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inflammation
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• Acute exercise can induce inflammation
• Duration, intensity-dependent
• Chronic exercise training may reduce systemic
  levels of inflammation reduce response to acute
  inflammatory event

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Concentration of serum interleukin-6 by amount of
weekly exercise in elderly adults
pgender, race Additionally adjusted for smoking,
alcohol, use of anti-inflammatory drugs, use of
antioxidant vitamins, diseases Additionally
adjusted for total body fat, visceral fat
Colbert et al., J Am Geriatr Soc, in press
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Concentration of serum CRP by amount of weekly
exercise in elderly adults
pgender, race Additionally adjusted for smoking,
alcohol, use of anti-inflammatory drugs, use of
antioxidant vitamins, diseases Additionally
adjusted for total body fat, visceral fat
Colbert et al., J Am Geriatr Soc, in press
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Concentration of serum CRP by quartile of
non-exercise physical activity among elderly
adults who do no exercise
pquartile Adjusted for age, gender, race
Additionally adjusted for smoking, alcohol, use
of anti-inflammatory drugs, use of antioxidant
vitamins, diseases Additionally adjusted for
total body fat, visceral fat
Colbert et al., J Am Geriatr Soc, in press
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Concentration of serum TNFalpha following a
5-month exercise training program
Tsukui et al., In J Obes, 2000
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Parameter estimates for PGE2 in rectal mucosa of
63 men and women with a history of polyps
Martínez et al., J Natl Cancer Inst, 1999
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From Ohshima et al., Arch Biochem Biophys, 2003
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Survival of colorectal cancer patients following
surgical resection by serum IL-6 concentration
From Chung Chang, J Surg Oncol, 2003
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Chronic inflammatory conditions associated with
neoplasms
Coussens Werb, Nature, 2002
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Cancers associated with infectious agents
Coussens Werb, Nature, 2002
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Relative risk of colon cancer according to
aspirin use (1984-1992), Nurses Health Study
Adjusted for age, family history, smoking, BMI,
physical activity, diet
Giovannucci et al., N Engl J Med, 1995
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Relative risk of incident cancer by baseline
plasma CRP level Womens Health Study
Matched for age smoking adjusted for treatment
assignment, BMI, diseases, exercise, family
history
Rifai et al., Arch Intern Med, 2002
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Epidemiologic and experimental studies somewhat
supportive
Evidence for site-specific inflammation Inflammati
on important for survival No evidence for general
inflammation incident cancer (1 study)
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IGF-1 and binding proteins
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Participation in Exercise by Level of IGF-1 in
Elderly Men and Women
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IGF-1 (mean SE) following 8 weeks of treadmill
exercise in Min mice
Colbert et al., Med Sci Sports Exerc, 2003
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Odds ratios for colon cancer by IGF-1 and IGFBP3
level
Matched for age, sex, date of blood collection,
fasting status, and adjusted for smoking
Palmqvist et al., Gut, 2002
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Odds ratios for prostate cancer by IGF-1 and
IGFBP3 level
Adjusted for age, fasting time, BMI, smoking
Stattin et al., J Natl Cancer Inst, 2000
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Incidence of cecum tumor growth in LID mice
a Control saline versus LID saline, P 0.01. b Control saline versus Control IGF-I,
P 0.01.
Wu et al., Cancer Res, 2002
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Human - both cross-sectional and experimental
studies are conflicting Animal little data yet
Human Epidemiologic evidence that IGF-1
increases cancer risk Animal IGF-1 treatment /
IGF-1 transgenics In vitro IGF-1 increases
proliferation, decreases apoptosis
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Obesity/Body Fat
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• Physical activity and Body weight/fat
• Physically active have lower levels of body
  weight and fat
• Exercise can reduce body weight and fat in
  animals, can help humans maintain weight loss
• Obesity and Cancer
• Obesity linked to colorectal, postmenopausal
  breast, endometrial and other cancers
• Weight gain in particular
• But does a change in body fat mediate any effect
  of physical activity on cancer incidence?

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Body composition of heterozygous p53 deficient
(p53/-) Wnt-1 transgenic mice by treatment group
(mean SE).
padjustment for multiple comparisons in Treadmill
expt) a adjusted for lean mass b adjusted for
total body mass c adjusted for fat mass (g)
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CONCLUSIONS

• Inflammation markers assoc with activity
  cancer?
• IGF assoc with activity? cancer probable
• Obesity assoc with activity assoc with cancer
  mediator?
• No confirmed mechanisms yet
• Multiple mechanisms probably at work

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Acknowledgements
NCI
NIA

• Stephen Hursting
• Volker Mai
• David Berrigan
• Jackie Lavigne
• Susan Perkins
• Lisa Birely

• Tamara Harris
• Marjolein Visser

AMC Cancer Research Center

• Kim Westerlind

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Concentration of serum CRP by exercise level and
use of antioxidant supplements (multivit, Vit C
or E, beta carotene)
no suppl use
suppl use
C-reactive protein (log mg/L)
Colbert et al., J Am Geriatr Soc, in press