obesity and cancer

Obesity and cancer

Kim Robien, PhD, RD, CSODepartment of Epidemiology and Biostatistics

Department of Exercise ScienceSchool of Public Health and Health Services

George Washington Universitykrobien@gwu.edu

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