Obesity and cancer

National Press Foundation, Cancer Program 2012

Kim Robien, PhD, RD, CSO

Department of Epidemiology and Biostatistics Department of Exercise Science School of Public Health and Health Services George Washington University krobien@gwu.edu

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

Medical Complications of Obesity

Pulmonary disease
abnormal function obstructive sleep apnea hypoventilation syndrome

Idiopathic intracranial hypertension Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Cancer
breast, uterus, cervix colon, esophagus, pancreas kidney, prostate

Nonalcoholic fatty liver disease

steatosis steatohepatitis cirrhosis

Gall bladder disease

Gynecologic abnormalities
abnormal menses infertility polycystic ovarian syndrome

Osteoarthritis Skin
Gout

Phlebitis
venous stasis

How big of a problem is obesity?

Obesity Trends* Among U.S. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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.

Obesity Trends* Among U.S. Adults BRFSS, 2002

(*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. Adults BRFSS, 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. Adults BRFSS, 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. 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%

Source: Behavioral Risk Factor Surveillance System, CDC.

Obesity Trends* Among U.S. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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. Adults BRFSS, 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.

Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010

(*BMI 30, or about 30 lbs. overweight for 54 person) 1990 2000

2010

No Data

<10%

10%14%

15%19%

20%24%

25%29%

30%

Source: Behavioral Risk Factor Surveillance System, CDC.

How do we measure obesity?

Body Mass Index

BMI = weight (kg)/ height (m2) NHLBI BMI Calculator:
Weight status category Under weight

http://www.nhlbisupport.com/bmi
BMI < 18.5

Healthy weight
Overweight Obese I Obese II Extreme obesity

18.5 24.9
25.0 29.9 30.0 34.9 35.0 39.9 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

Computed tomography (CT) Magnetic resonance imaging (MRI)

Considered the gold standard

Can quantify composition in specific body parts Can quantify composition in specific body parts

Limited availability Burdensome/traumatic for participants

Expensive Limited availability Expensive Limited availability Moderately expensive Limited availability

Dual X-ray Can quantify composition absorptiometry (DEXA) in specific body parts

Bioelectric impedence analysis (BIA)

BodPod Skin fold measurements

Portable

Somewhat expensive Highly dependent on hydration status, time of day

Moderately expensive Limited availability Not terribly accurate Significant variation between operators

Low participant burden Relatively inexpensive Portable

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: inflammation

Adipose 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, hormones

Obesity 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

Data from 19 prospective cohort studies, including 1.46 million white adults

Berrington de Gonzalez et al. New Engl J Med 2010, PMID: 21121834

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-Obesityin-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