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Colorectal Cancer: Do Health Habits Matter, and How Do Patients Lower Risk?

Robert S. Sandler, M.D., M.P.H.University of North Carolina at Chapel Hill

Chapel Hill, North Carolina

Colon cancer is a preventable disease

Background

Primary prevention of colon cancer

diet – meat, fiber, vegetables, minerals, vitamins

Outline

diet meat, fiber, vegetables, minerals, vitamins

habits – obesity, physical activity, constipation, smoking, alcohol

Recommendations

Strategy – new information; evidence-based

US Cancer Deaths, 2009

Other

Colon

Lung

Prostate

BreastLeukemia

OvaryLiver

KidneyBladder

Brain

Lymphoma* 146,970 new cases

49,920 deaths

American Cancer Society, 2009

Geographic variation

CA Cancer J Clin 2005; 55:74-108

UnitedStates

Migrants

Migrants from Southeast Asia to the United States acquire higher rates of colorectal cancer

Cancer & diet

2

Cancer & diet

World Cancer Research Fund, 2007

30

40

50

NZ

USA CAN

UK

Rat

e

Meat

0

10

20

0 50 100 150 200 250 300

Per capita daily meat consumption - grams

NIG

COL

JAP YUG FIN

SWE

R

From Int J. Cancer 1975:15:617

1500

2000

2500

1

1.25

1.5

storksbabies

odin

g st

orks

Ecological fallacy

500

1000

1500

1965 1970 1975 1980

0.25

0.5

0.75

pairs

of b

roo

Colorectal cancer incidence and red and processed meat consumption (highest vs. lowest categories), from 6 cohort studies

Meat

World Cancer Research Fund, 2007

1.21 (1.06-1.45)

Cooking meat at high temperatures produces heterocyclic amines and polyaromatic hydrocarbons

Meat Meat

3

Fiber

Denis Burkitt1911-1993

surgeon and geographical epidemiologist

Fiber

JAMA 2005;294:2849

Fiber

Study-Specific and Pooled Multivariate Relative Risks (RRs) of Colorectal Cancer Comparing the Highest vs the Lowest Quintile of Dietary Fiber Intake

JAMA 2005;294:2849-2857.

0.94 (0.86-1.03)

Vegetables

Phytochemicals

Natural product chemists have isolated over 100 compounds from the plant kingdom that are either antimutagenic or anticarcinogenic

carotenoids carrots yams watermelons

Phytochemicals

carotenoids carrots, yams, watermelons

terpenes citrus fruits

plant phenols grapes, strawberries, apples

thioethers garlic, onions, leeks

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Phytochemicals

Clin Gastro & Hepatology 2006;4:1035-38.

Phytochemicals

oly

p N

umbe

r

Clin Gastro & Hepatology 2006;4:1035-38.

months

Po

Garlic

Engraving of the Allium sativum plant, showing the bulb leaf, stem, and flower. From William Woodville, Medical Botany, 1793.

Garlic

World Cancer Research Fund, 2007

Calcium

Forest plot for colon cancer incidence and dietary calcium intake (highest vs. lowest category), from 9 cohort studies

World Cancer Research Fund, 2007

0.84 (0.74-0.95)

VOLUME 342 January 13, 1999 NUMBER 2

Calcium

Number of subjects with one or more polyps – 19% decreaseMean number of polyps per subject – 24% decrease

N Engl J Med 1999;340:101-7

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Vitamin D

JNCI 2007;99:1594-602

Colorectal cancer RR 0.28 (0.11-0.68)

JAMAThe Journal of the American Medical Association

Volume 276(24) 25 December 1996 pp 1957-1963

Effects of Selenium Supplementation for Cancer Prevention in Patients ith C i f th Ski A R d i d C t ll d T i l

Selenium

with Carcinoma of the Skin: A Randomized Controlled Trial

Larry C Clark, MPH, PhD, Gerald F. Combs, Jr PhD, Bruce W. Turnbull, PhD, Elizabeth H. Slate, PhD, Daniel K. Chalder, MD, James Chow, MD, Loretta S. Davis, MD, Renee A. Glover, MD, Gloria F. Graham, MD, Earl G. Gross, MD, Aaron Krongrad, MD, Jack L. Lesher, MD, H. Kim Park, MD, Beverly B. Sanders, Jr., MD, Cameron L. Smith, MD, Richard J. Taylor, MD

Conclusions: ...results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites.

Colorectal cancer RR: 0.42 (95% CI 0.18-0.95)

Anti-oxidants

“Well, so much for antioxidants.”

Anti-oxidants

Lancet 2004;364:1219-28

Effect of all antioxidants (vitamins A, C,E, B carotene, selenium alone or combination) on GI cancers

0.96 (0.88-1.04)

Folic acid

0.84 (0.76-0.93)

World Cancer Research Fund, 2007

Folic acid

JAMA 2007;297:2351-59.

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Risk Ratios Comparing Folic Acid vs. Placebo by Randomized Aspirin Treatment

Folic acid

JAMA 2007;297:2351-59.JAMA 2007;297:2351-59.

Folic acid

CEBP 2007;16:1325-9

Folic acid

CEBP 2007;16:1325-9

Majority of studies show smoking increases the risk of colorectal cancer

Induction latency period for cancer may be long, 30-40 years

Mechanism uncertain

Cigarette smoking

Mechanism uncertain

Forest plot for rectal cancer incidence and beer consumption (highest vs. lowest category), from 4 cohort studies

Alcohol (beer)

World Cancer Research Fund, 2007

1.33 (0.96-1.84)

Obesity

Portrait of Daniel Lambert by Benjamin Marshall, 19th

Century

At the time of Lambert’s deathAt the time of Lambert’s death in 1809 in Stamford, England, he was 39 years of age and weighed 739 pounds. The wall of the public house in which he was staying had to be dismantled to remove his body

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Obesity

1998

Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1998, 2006

1990

(*BMI ≥30, or about 30 lbs. overweight for 5’4” person)

2006

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity

Obesity

Colorectal Cancer (men BMI > 35) – odds ratio 1.84

N Engl J Med 2003;348:2197-9

Waist circumference

Int Journal Obesity 2004;28:559-67

Waist circumference is a stronger predictor of colon cancer risk than

is BMI

Height

Height and colorectal cancer, cohort studies

World Cancer Research Fund, 2007

1.09 (1.06-1.22)

Physical activity

Total physical activity and colorectal cancer, cohort studies

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Constipation Constipation

Am J Epidemiol 2000;151:958-64

Relative risk* of colorectal cancer according to bowel movement in a prospective study of women

bowel cancermovement (n=611)

>1/day 0.82

Constipation

1/day 0.82

Daily 1.00

Every 2 days 0.96

Every 3 days 0.94 (constipated)or less

* adjusted for age, body mass index, fiber intake, physical activity, postmenopausal status,hormone use, and laxatives

Am J Epidemiol 2000;151:958-64

Evidence Decreases Risk Increases Risk

Convincing Exercise Red/processed meatAlcohol

Cigarette smokingObesityHeight

Summary

Height

Probable GarlicCalciumSeleniumCurcumin

Limited VegetablesFiber

Antioxidants

Folic acid

What to recommend to patients

● Eat a sensible diet, high in vegetables, fruits and grains

● Limit red meat and processed meat

● Be as lean as possible without being underweight

B h i ll ti f t l t 30 i t d● Be physically active for at least 30 minutes a day

● Limit alcohol (2 drinks for men, 1 for women); don’t smoke

● Consider supplements with calcium (1200 mg/day) plus vitamin D

● Get a colonoscopy!

Kenan Stadium