Transcript Cancer Prevention

CANCER PREVENTION
Veronica McLymont, PhD, RDN, CDN
Memorial Sloan-Kettering Cancer Center
New York
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October 2014
HARTFORD HEALTHCARE CANCER
INSTITUTE
• Majority of cancer care in the US delivered by
community oncologists.
• Cancer advances can take years to be adopted
in a community setting.
• Requires a robust institutional clinical research
program, with patient access to cutting-edge
clinical trials, offering the newest therapeutic
options.
IMPLICATIONS OF AGE AND AGING
With the increasing life
expectancy, the numbers of
cancer cases and mortality
are rising.
Cancer, 2002
ESTIMATED NEW CANCER CASES & DEATHS
IN THE U.S. – 2013
• In 2014, there will be an estimated
1,665,540 new cancer cases
diagnosed
• 585,720 cancer deaths in the US.
• Cancer remains the second most
common cause of death in the US,
accounting for nearly 1 of every 4
deaths
ACS, 2013
THE BURDEN OF CANCER
The growing burden of
cancer and other chronic
illnesses may outgrow the
capacity of the medical
services
Lancet Onc. 2011
CAUSES OF CANCER
•
•
•
•
•
Smoking
Diet/obesity
Sedentary Life Style
Alcohol
Infection/inflammation
HPV, Helicobacter, Hepatitis, HIV
• Sun Exposure
• Medical Therapies
• Genetic Syndromes
The impact of environmental exposure is partially dependent on the
person’s genetic make up.
Rate / 100,000 population
AGE-ADJUSTED CANCER DEATH RATES,
FEMALES BY SITES, U.S. 1930 – 2009
45
40
35
30
25
20
15
10
5
0
Lung
Cervix
Stomach
ACS, 2013
ESTIMATED NEW CANCER CASES AND DEATHS
U.S. 2013
250,000
200,000
150,000
New Cases
Deaths
100,000
50,000
Colorectal
0
Lung &
Bronchus
Colorectal Breast Pancreas Prostate Esophagus Stomach Oral cavity &
Pharynx
ACS 2013
ACTUAL CAUSES OF DEATH IN THE US
Poor diet and physical inactivity may
soon overtake tobacco as the leading
cause of death.
Mondadori, Marks, Stroup, Gerberding, JAMA, 2000
DIET OBESITY AND CANCER
ADULT OBESITY A GLOBAL VIEW
Percent
of Adults
with
obesity
WHO 2014
(most recent data available for each country)
MICHELANGELO’S DAVID
AFTER A SHORT STAY IN AMERICA
PREVALENCE OF CHILDHOOD OBESITY
IN THE US
• More than doubled in children and
quadrupled in adolescents in the past 30
years.
• The percentage of obese children age
6–11 years increased from 7% in 1980 to
nearly 18% in 2012.
Ogden, et al (2014) JAMA
Cancer Risk and Obesity
MALE
FEMALE
http://www.cancer.net/sites/cancer.net/files/obesity_infographic.pdfbijhbjn
IGF-1 and Subacute
Inflammation
http://www.cancer.net/sites/cancer.net/files/obesity_infographic.pdfbijhbjn
IGF-1 and Subacute
Inflammation
http://www.cancer.net/sites/cancer.net/files/obesity_infographic.pdfbijhbjn
Estrogen and Adipocytes
http://www.cancer.net/sites/cancer.net/files/obesity_infographic.pdfbijhbjn
Estrogen and Adipocytes
http://www.cancer.net/sites/cancer.net/files/obesity_infographic.pdfbijhbjn
POTENTIAL MECHANISMS OF OBESITY
CARCINOGENIC EFFECT
OBESITY
INSULIN/IGF
LIPID SIGNALING MOLECULES
CHANGES IN INTESTINAL
MICROBIOTA
PLATLET ACTIVATING FACTOR
PROSTAGLANDINES
???
INFLAMATION/CYTOKINES
TNF-, IL-6
CARCINOGENIC EFFECT
OBESITY SIGNIFICANTLY INCREASED
THE RISK OF PANCREATIC CANCER.
In 2 prospective cohort studies,
physical activity appears to decrease
the risk of pancreatic cancer
especially among those who were
overweight.
Michaud et al, JAMA 2001
CALORIC CONSUMPTION,
OBESITY, AND CANCER
INHIBITION OF INDUCED TUMORS IN MICE BY CALORIE RESTRICTION
Sarcomas
35
controls
30
25
20
15
calorie restricted
10
5
10
20
30
40
50
Number of mice with cancer
Number of mice with cancer
Epithelial Tumors
40
controls
35
30
25
calorie restricted
20
15
10
5
60
10
Number of weeks
20
30
40
50
60
Number of weeks
Cancer Research 1942;2:460
Estimates indicate that
50% of cancers are
preventable
Sc. Trans. Med. 2012
AN INTEGRATED STRATEGY FOR
CANCER
PREVENTION
AND
EARLY DETECTION
CANCER PREVENTION AND EARLY
DETECTION
1) Screening
2 ) Habits and Lifestyle
Nutrition
Exercise
Non-smoking
Sun Protection
3) Family history and Genetics
4) Vaccination, treatment of chronic infections
5) Attention to early signs and symptoms
SCREENING
General Population
Colon
Breast
Cervix
Prostate
High Risk Population
Lung
Oral Cavity
Esophagus
Liver
Skin
SCREENING FOR PREVENTION AND EARLY
DETECTION OF CANCER
Colorectal Cancer
•
•
•
•
•
Colonoscopy
Occult Blood in Stool
Sigmoidoscopy
CT colonography
DNA stool testing
* Women and men age 50 years and above
* Proven reduction in mortality
SCREENING FOR PREVENTION AND
EARLY DETECTION OF CANCER
Cervical Cancer
• Cervical cancer is the second most common
cancer among women worldwide.
• 274,000 deaths annually, 80% in developing
countries.
Screening
Pap Smear
Prevention
HPV Vaccine
SCREENING FOR EARLY DETECTION OF
CANCER
Breast Cancer
• Mammography
• Clinical examination
* Women age 40 years and above
* Proven reduction in mortality
FAMILY HISTORY/ GENETICS
•
•
•
Family History Evaluation
Genetic Testing
Genetic Counseling
PREVENTIVE MEASURES
•
INTENSIVE SCREENING
(EARLIER, MORE FREQUENT, ADDITIONAL TESTS)
•
•
PROPHILACTIC SURGERY
CHEMOPREVENTION
NUTRITION AND CARCINOGENESIS
NUTRITION AND CARCINOGENESIS
•
•
•
•
•
•
•
Calories
Nutrients
Non-nutritive components
Food preparation
Timing of diet
Gene –nutrient interaction
Interaction with other
environmental factors
THE POLYP PREVENTION TRIAL
Intervention:
Low fat, high fruit, vegetable, and fiber diet: 4 years
End Point :
Adenoma Recurrence:
Control Group
(N = 947)
No. of Adenomas
Advanced Adenomas
Intervention Group
(N = 958)
374
66
380
60
Schatzkin et al, NEJM, 2000
CAUSES OF CANCER: INHERITANCE AND
ENVIRONMENT
Scandinavian twin cohort studies
9,512 pairs with at least 1 cancer
Inheritance
Shared
environment
Non-shared
environment
stomach
0.28
0.10 (0-0.34)
0.62 (0.49-0.76)
colorectum
0.35 (0.10-0.48)
0.05 (0-0.34)
0.60 (0.52-0.70)
lung
0.26 (0-0.49)
0.12 (0-0.34)
0.62 (0.51-0.73)
breast
0.27 (0.00-0.41)
0.06 (0-0.22)
0.67 (0.59-0.76)
0.42 (0.29-0.50)
Inheritance
0 environment
(0-0.09)
shared
prostate
cervix
0
(0.10-0.51)
(0-0.42)
0.20 (0-0.35)
0.58
(0.50-0.67)
non
shared
0.82 (0.57-0.97)
Lichtenstein, et al NEJM 343:78,
2000
BENEFITS OF A HEALTHY
LIFESTYLE
HABITS AND LIFESTYLE
Good
Bad
BENEFITS OF A HEALTHY LIFESTYLE
Features:
•
•
•
•
Traditional Healthy Mediterranean diet
Non-smoking
Normal BMI
Physical activity
Least to most-healthy lifestyle
Women
15 yrs
Men
8.4 yrs
Am J Clin Nutri, 2011
Seven Countries Study - 1950s
MEDITERRANEAN DIET AND MORTALITY
Reduced mortality from: coronary heart disease, cancer.
Hu (2003) NEJM
MEDITERRANEAN DIET, CHD, AND
CANCER
• Despite a high fat intake, the
population of Crete had very low rates
of CHD and certain types of cancer
• Had a long life expectancy.
Hu, (2003) NEJM
AICR
RECOMMENDATIONS
AICR, 2007
BODY FATNESS
Be as lean as possible within the normal rage of body weight
• Ensure body weight through
childhood and adolescent
growth, projects towards the
lower end of the normal BMI
range at age 21.
• Maintain body weight within
the normal range from age
21
• Avoid weight gain and
increases in waist
circumference throughout
adulthood
Physical Activity
Be physically active as part of everyday life
• Be moderately physically
active, equivalent to brisk
walking for at least 30
minutes every day
• As fitness improves, aim for
60 minutes or more of
moderate, or for 30 minutes
or more of vigorous physical
activity every day.
• Limit sedentary habits such
as watching television
PHYSICAL ACTIVITY AND RISK OF
COLON AND BREAST CANCER
• Physical activity reduces risk (20-30%)
• Beneficial effects regardless of BMI
• Average activity: 30-60 minutes per day of
moderate to vigorous exercise
JAMA, 2003
Med, Sci in Sports Medicine, 2003
FITNESS THE WRONG WAY
FOOD AND DRINKS THAT PROMOTE WEIGHT GAIN
Limit consumption of energy-dense foods
Avoid sugary drinks
• Consume energy-dense
foods sparingly
• Avoid sugary drinks
• Consume ‘fast foods’
sparingly, if at all
PLANT FOODS
Eat mostly foods of plant origin
•
Eat at least five portions/servings
(at least 14 oz) of a variety of nonstarchy vegetables and of fruits
every day.
•
Eat relatively unprocessed cereals
(grains) and/or pulses (legumes)
with every meal
•
Limit refined starchy foods
•
People who consume starchy roots
or tubers as staples also to ensure
intake of sufficient non-starchy
vegetables, fruits and pulses
(legumes)
NON-STARCHY VEGETABLES/FRUITS
I
• Dietary fiber,
carotenoids,
folate selenium,
glucosinolates,
dithiolthiones,
indoles,
coumarins,
ascorbate,
antioxidants,
chlorophyll,
flavonoids,
allylsulphides,
phytoestrogens.
DIFFICULT TO UNRAVEL THE RELATIVE
IMPORTANCE OF EACH CONSTITUENT
Likely that protective effects may
result from a combination of
influences on several pathways
involved in carcinogenesis.
AICR, 2007
ANIMAL FOODS
Limit intake of red meat and avoid processed meat
People who eat
red meat to
consume less
than (18 oz) a
week, very little if
any to be
processed
Heme iron – N-nitroso
compounds
PRESERVATION, PROCESSING, PREPARATION
Limit consumption of salt
Avoid moldy cereals (grains) or pulses (legumes)
• Avoid salt-preserved, salted, or
salty foods; preserve foods
without using salt
• Limit consumption of processed
foods with added salt to ensure
an intake of less than 6 g (2.4 g
sodium) a day
• Do not eat moldy cereal (grains)
or pulses (legumes)
• Minimize exposure to aflatoxins
from moldy cereals (grains) or
pulses (legumes)
DIET AND STOMACH CANCER
Risk
Salt
Nitrosamines
Frying food
Obesity
Alcohol
Helicobacter pylori
Cigarette smoking
Risk
Fruits and vegetables
Vitamin C
ß carotene
WJ Gastro 2006, 28:12:5772
Carcinogenesis 2006, 27:1497
Carcinogenesis 2006, 27:2250
European J Can Pr 2000, 9:291
COOKING AND CARCINOGENESIS
Compounds formed during cooking cause
tumors in rodents:
• HeteroCyclic amines:
from heating protein
• Polycyclic aromatic hydrocarbons: from charring meat
• Nitrosamines:
from nitrogen oxide in flames
• Epoxides/
Hydroperoxides:
from heating fat
THE CORREA PATHOLOGICAL STEPS LEADING TO STOMACH CANCER
Normal gastric mucosa
H. pylori
salt
Superficial gastritis
Chronic inflammation
Other nutritional
factors
Recruitment of bone
marrow-derived stem cells
Atrophic gastritis
Higher gastric PH
Intestinal metaplasia and SPEM
Bacterial overgrowth and
nitrate production
Salt
B-Carotene
Dysplasia
Ascorbic acid
N-nitroso carcinogens
Chronic inflammation and
reactive oxygen species
Carcinoma
J Clin Investigation 2007
COOKING AND CARCINOGENESIS
STOMACH CANCER AMONG JAPANESE IN HAWAII
•
220 Japanese stomach cancer pts and 440 controls in
Hawaii.
• Migrants with the highest cancer risk in Japan continued
to display excess cancer risk long after they moved to
Hawaii
• Effect not seen among offsprings.
• Shows critical effect of early exposures.
• Elevated risks for both groups noted for users of pickled
vegetables and dried salted fish.
Haenszel, et al. (1972) JNCI
RED MEAT CONSUMPTION AND RISK OF
CANCERS - SWEDISH MAMMOGRAPHY
COHORT STUDY
• High consumption PDF processed meats
may increase the risk of stomach cancer.
• Dietary nitrosamines may be responsible.
Larsson, Bergkvist, Wolk, (2006) Int. J. Ca
.
ALCOHOLIC DRINKS
Limit alcoholic drinks
• If alcoholic drinks
are consumed,
limit consumption
to no more than
two drinks a day
for men and one
drink a day for
women
ALCOHOL AND CANCER
RISK
Increased:
• Mouth
• Esophagus
• Throat
• Liver
• Breast
Prostaglandins
AICR, 2013
TOBACCO SMOKING
Do not
smoke
NUMBERS OF U.S.DEATHS FROM BEHAVIORAL CAUSES, 2000
450
435
400
365
350
300
250
200
150
85
100
50
0
43
29
20
Sexual
Behavior
Alcohol
Motor
Vehicle
Guns
17
Drug
Induced
Obesity and
Inactivity
Smoking
JAMA 2004;291:1238-45
APPLYING WHAT WE KNOW TO
ACCELERATE CANCER PREVENTION
DIETARY SUPPLEMENTS
Aim to meet nutritional needs through diet alone
• Dietary
supplements are
not recommended
for cancer
prevention
EFFECT OF ANTIOXIDANTS AND VITAMINS
SUPPLEMENTS ON GI CANCER
• 14 randomized studies, (n= 170,525)
• Conclusion: “We could not find evidence that
antioxidant supplements can prevent
gastrointestinal cancer on the contrary, they seem
to increase overall mortality.”
Lancet 364, 1219, 2004
BREASTFEEDING
Mothers to breastfeed; children to be breastfed
• Cohort studies showed
statistically significant
decreased risk of obesity
with breast feeding.
• Aim to breastfeed infants
exclusively up to six
months and continue with
complementary feeding
thereafter eased risk of
obesity with
breastfeeding.
CANCER SURVIVORS
Follow recommendations for Cancer
Prevention
All cancer survivors to receive
nutritional care from an
appropriately trained professional
If able to do so, and unless otherwise
advised aim to follow the
recommendations for diet, healthy
weight, and physical activity.
APPLYING WHAT WE KNOW TO ACCELERATE
CANCER PREVENTION
Estimates based on a broad
range of scientific evidence
indicate that more than 50% of
cancers can be prevented.
Wolin, (2012), Science Translational Medicine
REDUCING THE MORBIDITY AND
MORTALITY CAUSED BY CANCER IS A
GLOBAL PRIORITY
Many patients with cancer
would otherwise experience
decades of good health.
Sullivan et al. Lancet 2011
WELLNESS IN THE 12TH CENTURY
Nutrition:
A person should never eat except
when he is hungry.
Exercise:
A person shall perform a physical
task or tire oneself by some other
form of exercise.
Stress Management:
He should not postpone his
elimination for even a single
moment.
I guarantee anyone who conducts himself according to
the directions…will not be inflicted with illness…He will
not require a physician… unless he became accustomed
to one of the bad habits.
M. Maimonides
F. Rosner “The Medical Legacy of Moses Maimonides” KTAV PUB.
House 1998
TAKE HOME MESSAGE
STRATEGIES FOR CANCER
PREVENTION AND EARLY DETECTION
1) Screening
2) Habits and Lifestyle
Nutrition
Exercise
Non-smoking
3) Family history and Genetics
4) Attention to early signs and symptoms