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As presented by: Kim Robien, PhD, RD, CSODepartment of Epidemiology and BiostatisticsDepartment of Exercise ScienceSchool of Public Health and Health ServicesGeorge Washington University
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Obesity and cancer
Kim Robien, PhD, RD, CSODepartment of Epidemiology and Biostatistics
Department of Exercise ScienceSchool of Public Health and Health Services
George Washington [email protected]
National Press Foundation, Cancer Program 2012
Obesity• Defined as the presence of excess body fat
• Adipose tissue is metabolically active and critical to health– Storage of energy for periods of fasting– Cushioning to protect organs and bones from injury– Important for maintaining body temperature– Endocrine functions: production of hormones such as leptin,
adiponectin, angiotensin, estradiol– Involved in production of other important proteins: aromatase,
cytokines
• Not all body fat is equal: visceral fat may be more metabolically active than subcutaneous
Pulmonary diseaseabnormal functionobstructive sleep apneahypoventilation syndrome
Nonalcoholic fatty liver diseasesteatosissteatohepatitiscirrhosis
Coronary heart disease Diabetes Dyslipidemia Hypertension
Gynecologic abnormalitiesabnormal mensesinfertilitypolycystic ovarian syndrome
Osteoarthritis
Skin
Gall bladder disease
Cancerbreast, uterus, cervixcolon, esophagus, pancreaskidney, prostate
Phlebitisvenous stasis
Gout
Medical Complications of ObesityIdiopathic intracranial hypertension
Stroke
Cataracts
Severe pancreatitis
How big of a problem is obesity?
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1985
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1986
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1987
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1988
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1989
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1990
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1991
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1992
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1993
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1994
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1995
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1996
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1997
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1998
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 1999
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2000
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% ≥20%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2001
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Source: Behavioral Risk Factor Surveillance System, CDC.
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
Obesity Trends* Among U.S. AdultsBRFSS, 2002
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2003
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2004
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2005
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2006
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2007
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2008
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2009
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. AdultsBRFSS, 2010
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
2000
Obesity Trends* Among U.S. AdultsBRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2010
1990
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
How do we measure obesity?
Body Mass Index
BMI = weight (kg)/ height (m2)
NHLBI BMI Calculator: http://www.nhlbisupport.com/bmi
Weight status category BMI
Under weight < 18.5
Healthy weight 18.5 – 24.9
Overweight 25.0 – 29.9
Obese I 30.0 – 34.9
Obese II 35.0 – 39.9
Extreme obesity ≥ 40.0
BMI
Strengths:• Provides a more accurate measure of total body fat compared with
the assessment of body weight alone.• Inexpensive, easily calculated• Most practical method of assessing body composition for large
epidemiologic studies.
Limitations:• Overestimates body fat in persons who are very muscular.• Can underestimate body fat in persons who have lost muscle mass
(example: many elderly)
Location, location, location
Subcutaneous fat – fat deposits just beneath the skin– Most highly correlated with insulin resistance (PMID: 8922352,
7615840, 9313753)
Visceral fat – fat deposits in the peritoneal cavity, surrounding internal organs
– Excess visceral fat has been associated with insulin resistance, hyperlipidemia, hypertension, cardiovascular disease, and certain forms of cancer.
Waist circumference• Most practical tool to assess abdominal fat
• Fat in the abdominal region is associated with a greater health risk than peripheral fat (gluteal-femoral region)
• Abdominal fat appears to be an independent risk predictor for type 2 diabetes, dyslipidemia, hypertension, and CVD in patients with a BMI of 25 - 34.9 kg/m2.
• For individuals with BMI ≥ 35, waist circumference adds little to the predictive power of the disease risk classification of BMI.
Other methods of measuring body composition (primarily used in research)
Method Strengths Limitations
Hydrostatic (underwater) weighing
Considered the gold standard
Limited availabilityBurdensome/traumatic for participants
Computed tomography (CT)
Can quantify composition in specific body parts
ExpensiveLimited availability
Magnetic resonance imaging (MRI)
Can quantify composition in specific body parts
ExpensiveLimited availability
Dual X-ray absorptiometry (DEXA)
Can quantify composition in specific body parts
Moderately expensiveLimited availability
Bioelectric impedence analysis (BIA)
Portable Somewhat expensiveHighly dependent on hydration status,
time of day
BodPod Low participant burden Moderately expensiveLimited availability
Skin fold measurements
Relatively inexpensivePortable
Not terribly accurateSignificant variation between operators
Obesity and cancer
BMI and cancer risk
Renehan et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569-578. PMID: 18280327
World Cancer Research Fund (2007)
Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective
• Systematic review of the nutrition, physical activity and cancer literature
• Detailed review of the evidence supporting an association between obesity and cancer risk.
• Entire document can be downloaded for free: www.dietandcancerreport.org
• Continuous Update Project is underway
“Maintenance of a health weight throughout life may be one of the most important ways to protect against cancer”
Possible biologic mechanisms: inflammationAdipose cells (adipocytes) synthesize and release a variety of proteins that mediate the inflammatory response, such as C-reactive protein, adiponectin, tumor necrosis factor-alpha, interleukins and adhesion molecules.
Chronic inflammation, which lasts for weeks, months, or longer, can cause lasting damage to many body tissues by:
• generating excess reactive oxygen species (ROS) and reactive nitrogen species (RNS), and lipid peroxidation (LPO)
• leading to tissue and DNA damage (PMID: 16909291, 20840865)
Elevated C-reactive protein levels have been associated with increased risk of colorectal, breast, ovarian, pancreatic, and lung cancers (PMIDs: 19190628, 18528865, 17667994, 19301134, 22912790)
Possible biologic mechanisms: growth factors, hormonesObesity can cause peripheral insulin resistance
• In addition to stimulating the liver to produce more insulin, high blood sugars can directly damage tissues
• Insulin and insulin-like growth factor levels are commonly elevated in obese individuals
Cancer cells express insulin and insulin-like growth factor receptors
Insulin and insulin-like growth factors activate signaling pathways in cancer cells leading to growth and proliferation (PMID: 22337149)
Inflammation increases expression of aromatase in adipose tissue (PMID: 22169755), increasing local estrogen production.
Possible biologic mechanisms: growth factors, hormones
Parekh et al, PMID: 22540252
Possible biologic mechanisms: storage site for environmental toxins
• Persistent organic pollutants – Polychlorinated biphenols (PCB)– Dichlorodiphenyltrichloroethane (DDT)– Dioxins
• Heavy metals (mercury, arsenic, cadmium, lead)• Vitamin D
PMID: 18035514, 19858070
Obesity may influence cancer screening behaviors
• Morbidly obese women are significantly less likely to report recent mammography (PMID: 19277790)
• Obese white women are less likely to report being screened for cervical cancer than their lean counterparts, and this does not hold true for black women (PMID: 18997682)
• BMI was not associated with colon cancer screening (PMID: 22492832)
Obesity and cancer survival
Obesity and survival after a cancer diagnosis
People who are overweight/obese at cancer diagnosis tend to have poorer outcomes
• Associations between obesity and cancer recurrence
• Increased risk of complications following surgical resection
• Unclear how to dose chemotherapy for overweight and obese patients
Cancer-specific mortality by BMI
Berrington de Gonzalez et al. New Engl J Med 2010, PMID: 21121834
Data from 19 prospective cohort studies, including 1.46 million white adults
Obesity and breast cancer survival
Protani et al. PMID: 20571870
Obesity and prostate cancer survival
Relative risk per 5 kg/m2 increase in BMI and prostate-cancer specific mortality. Cao and Ma 2011, PMID: 21233290
IOM Conference on Obesity and Cancer Survival and Recurrence
http://www.iom.edu/Reports/2012/The-Role-of-Obesity-in-Cancer-Survival-and-Recurrence.aspx
Report available as a free PDF download from the National Academies Press
http://www.nap.edu/catalog.php?record_id=13348
Summary article published in Cancer Epidemiology Biomarkers and Prevention, August 2012 PMID: 22695735