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Byers opac2013
1. population science
and clinical research
Tim Byers MD MPH
University of Colorado Cancer Center
Colorado School of Public Health
Tim.Byers@ucdenver.edu
2. This year there will be more deaths
in the World from cancer than from:
3. This year there will be more deaths
in the World from cancer than from:
Malaria
4. This year there will be more deaths
in the World from cancer than from:
Malaria
Tuberculosis
5. This year there will be more deaths
in the World from cancer than from:
Malaria
Tuberculosis
HIV
6. This year there will be more deaths
in the World from cancer than from:
Malaria
Tuberculosis
HIV
Childhood diarrhea
7. This year there will be more deaths
in the World from cancer than from:
Malaria
Tuberculosis
HIV
Childhood diarrhea
Combined
8. Deaths in the World in 2010
• Cancer 8,000,000
• Diarrhea 1,400,000
• HIV 1,500,000
• TB 1,200,000
• Malaria 1,200,000
• IHD 7,000,000
• Stroke 5,900,000
• COPD 2,900,000
9. Global importance
of obesity and cancer
• Cancer is the leading cause of death
• Obesity is pandemic (global fattening)
• Obesity is a (the) leading cause of
cancer
14. Larry Garfinkel 1922 to 2010
Pioneer in obesity and cancer epidemiology
Lew EA, Garfinkel L.
Variations in mortality by weight among 750,000 men and women.
J Chronic Dis. 1979;32(8):563–576
15. Discovery and re-discovery of the
obesity and cancer relationship
• Larry Garfinkel (ACS CPS-1 1970’s)
• Jean Calle (ACS CPS-1 paper in NEJM 1999)
• IARC Report 2002
• Jean Calle (ACS CPS-2 paper in NEJM 2003)
• WCRF Report 2007
17. Challenges for WCRF
• Nutrition is complex
» Foods
» Nutrients
» Preparation methods
» Additives and contaminants
» Energy balance
• The volume of literature is large
• Different factors in different populations
20. Obesity may be the most
important of all the nutritional
risk factors for cancer
• Many sites
• Men and women
• Preventable
• Modifiable
21. WCRF estimates of
preventable fraction of
cancers from obesity
United States 20%
United Kingdom 17%
Brazil 13%
China 12%
22. WCRF estimates of the preventable
fraction of cancers from obesity in U.S.
Breast 17%
Endometrial 49%
Esophagus 35%
Colorectum 9%
Pancreas 28%
Gall bladder 21%
Kidney 24%
All above sites 20%
23. WCRF recommendations
1. Avoid being overweight
2. Be active
3. Eat less energy dense foods
4. Eat more plants
5. Eat less meat
6. Drink little or no alcohol
7. Avoid poorly preserved foods
8. Do not rely on nutritional supplements
9. Breastfeed
10. Cancer survivors: as above
24. WCRF body weight
Recommendations
•Be as lean as possible within the normal range of body weight
•Through childhood and adolescence
project toward the lower end of
normal body weight (BMI 18.5)
•Throughout adulthood stay within the
normal range of body weight (BMI <25)
•Avoid weight gain and increases in
waist circumference in adulthood
26. Mechanisms linking
obesity and breast cancer
• Estrogens
• SHBG
• Cytokines ?
• Insulin ?
• IGF / IGFBP3 ?
• Innocent bystander ?
– Probably not
27. Obesity and risk of breast
cancer recurrence
• Recurrence risk increased among obese
(BMI > 30) vs normal weight (BMI<25)
• Obesity risk seen in various subgroups
– Postmenopausal BMI <25
– Premenopausal % recurrence free
– ER positive BMI >30
– ER negative
– WithTamoxifen
weeks
28. How can we know that weight
loss will reverse cancer risk?
29. How can we know that weight
loss will reverse cancer risk?
• Observational epidemiology
30. How can we know that weight
loss will reverse cancer risk?
• Observational epidemiology
• Randomized controlled trials
– (large trials with cancer endpoints)
31. How can we know that weight
loss will reverse cancer risk?
• Observational epidemiology
• Randomized controlled trials
– (large trials with cancer endpoints)
• Understanding of intermediary factors
– (proof of their modulation in small trials)
41. BMI
Intermediaries
Micronutrients
Hormones
Other growth factors
Inflammation
Immune function
Cancer
42. BMI
Diet
Intermediaries
Micronutrients
Hormones
Other growth factors
Inflammation
Immune function
Activity
Cancer
43. How can we determine
causal pathways?
• Measure effect modification
– Works only for strong associations
• Conduct interventions
– Modulate weight and measure mediators
– Modulate mediator and measure effects toward
cancer
•
44. How can we determine
causal pathways?
• Measure effect modification
– Works only for strong associations
• Conduct interventions
– Modulate weight and measure mediators
– Modulate mediator and measure effects toward
cancer
• Draw pictures
– Combining imagination and PowerPoint is scientifically
dangerous
45. Correlates of obesity
• Behavioral
– Diet
– Physical activity
– Medical care
• Physiologic
– Hormonal
– Other growth factors
– Inflammation
– Micronutrients
46. RCT’s of intentional weight loss
and changes in cytokines
• IL-6
• TGF-alpha
• Leptin
• Adiponectin
• CRP
• others
Byers T and Sedjo R Diabetes Obesity and Metabolism 2011 13:1063-72
47. CRP reduction with weight loss
0 5 10 15 20 25 30 35 40
0
10
20
% CRP reduction
30
40
50
60
70
80
90
100
% body weight loss
Byers T and Sedjo R Diabetes Obesity and Metabolism 2011 13:1063-72
48. Why do we need to
understand obesity-cancer
intermediaries?
• Fill holes in our understanding of biology
• Identify targets for prevention
49. Why do we need to be
skeptical about obesity-
cancer intermediaries?
• Changing intermediaries many times does
not change risk of disease
• Remember HLD
50. My recommendations
for research
• Find better ways to reduce obesity
• Prove reversibility
• Better understand the mechanisms and
test their change in focused trials
• Find ways to unlink obesity and cancer
54. Policy opportunities for
reversing global fattening
• Convergence of evidence for
cancer, heart disease, diabetes
• Collaboration across
governments and NGOs
55. United Nations General Assembly 16 September 2011
Political declaration of the High-level Meeting of the General
Assembly on the Prevention and Control of NCDs
1. Acknowledge that the global burden and threat of non-communicable
diseases constitutes one of the major challenges for development in the
twenty-first century, which undermines social and economic development
throughout the world, and threatens the achievement of internationally
agreed development goals;
2. Recognize that non-communicable diseases are a threat to the
economies of
many Member States, and may lead to increasing inequalities between
countries and populations;
3. Recognize the primary role and responsibility of Governments in
responding
to the challenge of non-communicable diseases and the essential need for
the efforts
56. “For prevention you have to do
the right thing….
….and enough of it.”
Pekka Puska
58. population science
and clinical research
Tim Byers MD MPH
University of Colorado Cancer Center
Colorado School of Public Health
Tim.Byers@ucdenver.edu
