Transcript Diet and Cancer

Diet and Cancer: Can Your Diet
Really Reduce Cancer Risk?
Tarek Elrafei, D.O.
Division Chief, Hematology/Medical Oncology
Jacobi Medical Center, Bronx NY
Assistant Professor
Albert Einstein college of Medicine
Cancer Prevention
• Diet
–
–
–
–
–
–
–
Dietary Fat
Red meat
Fruits and Vegetables
Dairy
Fiber
Glycemic load
Omega-3 fatty acids
• Vitamins & Micronutrients
• Alcohol
• Nutritional support in patients with cancer
American Cancer Society (ACS)
Recommendations for Individual Choices
Consume a healthy diet, with an emphasis on plant sources.
•Choose foods and beverages in amounts that help achieve and maintain a
healthy weight.
•Eat five or more servings of a variety of vegetables and fruits each day.
•Choose whole grains in preference to processed (refined) grains.
•Limit consumption of processed and red meats
If you drink alcoholic beverages, limit consumption.
•Drink no more than one drink per day for women or two per day for men.
CA Cancer J Clin 2006; 56:254-281
What’s the evidence?
• Pubmed search for “diet + cancer”
– 27,360 scientific publications
• Epidemiological, animal studies, retrospective,
prospective observational studies, clinical trials
– 961 Randomized controlled trials
– 128 Meta-analysis
– 32 practice guidelines
• Pubmed search for “Fava beans and
cancer”???
While we have come a long way since this 1940’s
Advertisement, we still can not identify who will and will not
benefit from dietary intervention strategies
Dietary Fat
• No clear link between total fat intake and colon
or breast cancer
– Womens Health Initiative Dietary Modification Trial
• 48,835 women followed for 8 years
– Behavioral modification program to reduce dietary fat: reduced
% calories consumed as fat 10.7% year 1 and 8 % at year 6
– vs.“usual diet” control group
– No difference in incidence of colon cancer; a trend towards
decreased breast cancer
• Prostate cancer
– Large amounts of alpha linoleic acid and low linoleic
acid increase risk (red meats and dairy)
– Mechanism of association may be lower testosterone
levels on men who decrease fat intake
Physicians Health Study
•
•
randomized trial of aspirin and β-carotene (vs.
placebo)
22,071 U.S. male physicians, ages 40 to 84 in
1982, without a history of cardiovascular
disease, cancer, or other major illnesses
•
14,916 U.S. male physicians provided plasma samples,
which were frozen at -82 degrees C:
•
Blood levels of all the trans-fatty acids examined for the
120 men who developed prostate cancer
Adjusted RR of nonaggressive prostate cancer by control quintiles of total 18:2n-6 trans-fatty
acids according to baseline BMI (A) and random aspirin assignment (B).
Chavarro J E et al. Cancer Epidemiol Biomarkers Prev
2008;17:95-101
©2008 by American Association for Cancer Research
Red Meat
•
Heme content, animal fat, carcinogens when meat is cooked at high
temperatures suggested to increase cancer risk
•
High intake of red meat including beef, pork, veal, and lamb, is
associated with an elevated risk of colorectal cancer in both men
and women in 6 studies…
– prospective study 47,949 U.S. male health professionals
•
•
•
•
•
205 cases of colon cancer after 6 years of follow up
Intakes of total fat, saturated fat, and animal fat were not related to risk of
colon cancer
Men who ate beef, pork, or lamb as a main dish five or more times per
week had a relative risk of 3.57 compared to men eating these foods <
once per month
Other sources of animal fat, including dairy products, poultry, and fish as
well as vegetable fat, were slightly inversely related to risk of colon cancer.
No clear association existed between fiber or vegetable intake and risk of
colon cancer.
Red Meat
•
prospective study 88,751 women 34 to 59
years
•
•
•
150 cases of colon cancer after 6 years of follow up
After adjustment for total energy intake, animal fat was
positively associated with the risk of colon cancer
The relative risk of colon cancer in women who ate beef,
pork, or lamb as a main dish every day was 2.49 as
compared with those reporting consumption < once a month
» Processed meats and liver were also significantly
associated with increased risk, whereas fish and
chicken without skin were related to decreased risk.
» A low intake of fiber from fruits appeared to contribute to
the risk of colon cancer, but this relation was not
statistically independent of meat intake
Red meat
• European Prospective Investigation into cancer
and nutrition (EPIC study)
– 478 040 men and women from 10 European countries
between 1992 and 1998.
– 1329 incident colorectal cancers were documented
after a mean follow-up of 4.8 years
– colorectal cancer risk is positively associated with
high consumption of red and processed meat and
support an inverse association with fish intake
Fruits and Vegetable
• A large number of potentially anticarcinogenic
agents are found in fruits and vegetables
• Retrospective studies and small prospective
studies have suggested a dose-response
relationship between fruit and vegetable intake
and the prevention of cancers.
– Soy decreases prostate cancer in men and breast
cancer in Asian women
– Flavonoids (tomatoes, green peppers, berries, and
citrus fruits) may decrease breast cancer
– Lycopene (tomatoes) may decrease prostate cancer
Epidemiologic Studies of
Lycopene and Cancer Risk
Cancer
Type of Study
Reference
Breast
Cohort
Dorgan et al.
Can Cau Cont 9: 89-97,
Case-control
Franceschi et al.
Int J Cancer 72:56-61,
Case-control
Agudo et al.
Eur J Cancer 33:1256-61,
Cohort
Giovannucci et al.
J Natl. Cancer Inst. 87:1767-76,
1995
1998
Colon
1997
Lung
1997
Prostate
Soy Intake and
Cancer
17 of 26 animal studies reveal soy or
soybean isoflavones reduce tumor
tumor development
19 or 21 human epidemiological studies
provide evidence of protection against
cancer, especially rectal and stomach
cancers (1 study reported increase)
Concerns
Growth enhancement of human mammary tumors transplanted into mice
that were fed soy or isoflavonids (Hsieh, et al. Cancer Res. 58:3833, 1998).
Soymilk Intake & Prostate
Cancer Risk
1.0
0.9
Relative Risk
0.8
0.3*
0
<1
1
>1
confidence interval 0.1-1.0
Daily Intake (servings)
Cancer Causes and Control 9: 553, 1998
Fruits and Vegetables
•
Large prospective studies have not found such a benefit:
– 71,910 women from the Nurses' Health Study and 37,725 men in the Health
Professionals' Follow-up Study found no association between fruit and vegetable
intake and risk of cancer (for an increment of five servings daily, relative risk [RR]
1.00, 95% CI 0.95 to 1.05)
– The European Prospective Investigation into Cancer and Nutrition (EPIC) study
examined the association between fruit and vegetable intake and risk of breast
cancer in 285,526 women ages 25 to 70.
• Comparing highest and lowest quintiles, there was no association with intake of fruits
(RR 1.09, 95% CI 0.94-1.25) or vegetables (RR 0.98, CI 0.84-1.14).
•
Conclusions and Interpretations
– there is a long lag time between exposures and the development of cancer,
during which time individuals may change their diets, limiting the power of
studies to detect effects
– Additionally, exposures in childhood may be more important in the
development of cancer than exposures later in life
– It is possible that intake of specific fruits and vegetables may have effects on
specific cancers.
Types of Bioactive Compounds May
Vary with New Varieties
Tomato Varieties
Dairy
• A meta-analysis of 21 studies evaluating the
relationship of dairy food intake and ovarian
cancer found no evidence of association in case
control studies (RR 0.96) but…
• Of 4 prospective cohort studies, 3 did
demonstrate increased risk of ovarian cancer
with high intake of dairy foods
• Netherlands Cohort Study on Diet and Cancer.
– 62 573 postmenopausal women participating in the
Netherlands Cohort Study.
– After 11.3 years of follow-up, data of 252 incident
epithelial ovarian cancer cases with no association
Dairy Intake and Breast Cancer
• Nurses Health Study
– 88,000 women
– Breast cancer risk inversely associated with Low-fat
dairy, calcium (from dairy) and vitamin D (non-dairy
intake) in premenopausal women but not
postmenopausal
• Pooled analysis of 8 prospective studies confirm
no association between dairy and breast
cancer in postmenopausal women
– 351,041 women, 7379 of whom were diagnosed with
invasive breast cancer during up to 15 years of followup
Int J Epidemiol. 2002
Feb;31(1):78-85
Dairy
• Dairy Food, Calcium, and Risk of Cancer in the
NIH-AARP Diet and Health Study
– Calcium intake, as determined by a food frequency
questionnaire, was associated with decreased total
cancer risk over seven years in women, but not in
men, in a large US cohort of 567,000 participants
aged 50 to 71
– A decrease in cancers of the digestive tract
(particularly colon cancer) with higher dairy food and
calcium intake was noted in both men and women
Fiber and Cancer
•
The relationship between fiber intake and colorectal cancer risk is unsettled.
–
–
No relationship was noted in the large observational Nurses' Health Study (N Engl J Med
1999 Jan 21;340(3):169-76 ).
In contrast, some large observational studies have found a reduced risk of colorectal
adenomas and cancer with increased fiber intake.
•
A systematic review of five studies involving a total of 4349 patients concluded that
there was no definitive evidence that increased dietary fiber reduces the incidence or
recurrence of adenomatous polyps within a two- to four-year period
•
Similarly, a pooled analysis of 13 prospective cohort studies (involving 725,628 men
and women followed for 6 to 20 years) found that dietary fiber intake was inversely
associated with the risk of colorectal cancer but the association was no longer
apparent after accounting for other dietary risk factors
–
–
–
One possible explanation is that the sources of dietary fiber differed across the various study
populations.
Other possible explanations are that the fiber intake in the Nurses' Health Study was
relatively low even in the participants in the highest quintile of intake, or that dietary fiber is a
marker for the intake of fruits, vegetables, and grains but is not actually protective in and of
itself
Diet-Gene interactions
Diet-Gene Interactions in Colon Cancer
p21+/+ AIN-76A Diet
Percent survival
100
p21+/- AIN-76A Diet
90
80
p21+/+ *Western Diet
70
p21-/- AIN-76A Diet
p21+/- Western Diet
60
50
40
p21-/- *Western Diet
30
20
10
0
0
4
8
12
16 Weeks
20 24
Yang et al, Cancer Res. 61, 565, 2001
28
32
36
*(high fat and
phosphate, low
calcium and
vitamin D)
Glycemic Load
• Glycemic load is a function of glycemic index,
carbohydrate content per serving, and frequency
of intake
– Glycemic Index = how rapidly and to what extent
blood glucose levels rise
• Insulin and Insulin like growth factors promote
cell proliferation and possibly certain cancers
• 15 studies (2.5 million patients) estimate 30%
higher risk of colon cancer among diabetics
Glycemic Load
• NIH-AARP Diet and Health Study
– 7 years of follow up
– found no association in 15,000 cancers in women and 33,000 cancers
cases in men
• Women’s Health Study
– 174 colon cancers in 38,451 women with a calculated 2.85 increased
risk
• Canadian trial
•
– 49 124 women participating in a randomized, controlled trial of
screening for breast cancer in Canada
– 16.5 years of follow-up, 616 incident cases of colorectal cancer and no
association of increased risk with higher glycemic index
Nurse’s Health Study & Health Professionals Follow up Studies
– 20 years of follow-up. 1,809 incident colorectal cancers
–
found no association for women but an increased risk for men of colon
cancer
Omega-3 Fatty Acids
• Individual studies have found increased
and decreased risk of cancer with no
consistent pattern
• Systematic Review of all prospective trials
revealed no association between Omega3 FA and cancer
– 20 cohorts from 7 countries for 11 different
cancer types
– 700,000 patients
Vitamins and Micronutrients
• National Institutes of Health (NIH)
consensus conference panel concluded
that…
– "present evidence is insufficient to
recommend either for or against the use of
multivitamin supplements by the American
public to prevent chronic disease"
Prostate Cancer Prevention Selenium and
Vitamin E
Cancer Prevention Trail (SELECT) ($175M)
35,000 men, age >55 (> 50 for Black Men)
Selenium 200 ug/d
Vitamin E 400 mg/d
Vitamin E
Selenium
Placebo
7 + Years Treatment
Endpoint Prostate Cancer Incidence
SELECT Trial
• SELECT stands for the Selenium and Vitamin E Cancer Prevention
Trial, a prevention clinical trial to see if one or both of these dietary
supplements prevent prostate cancer.
• SELECT is continuing to evaluate the effects of the supplements but
participants are no longer taking study supplements. The
independent Data and Safety Monitoring Committee for the trial
found that selenium and vitamin E, taken alone or together for an
average of five and one-half years, did not prevent prostate cancer.
• The SELECT data showed two concerning, but not statistically
significant, trends: there were slightly more cases of prostate cancer
in men taking only vitamin E and slightly more cases of diabetes in
men taking only selenium. Neither of these findings proves an
increased risk from the supplements and may be due to chance.
http://www.cancer.gov/newscenter/qa/2008/selectqa
Vitamins and Micronutrients
• Vitamin D may reduce colon cancer risk by
improving calcium absorption
• Prostate and Breast Cancer: Vit. D +
calcium showed no effect on breast cancer
in 3 trials
• One randomized prospective trial of
calcium + vit D in 1179 women over 4
years has shown decrease in all cancer
types
Am J Clin Nutr. 2008 Mar;87(3):794
Alcohol
Obesity and EBC Outcomes
• Obesity (BMI > 30) associated with poorer DFS and OS
in operable breast cancer
• Evaluation of women with EBC in adjuvant trials of
doxorubicin, cyclophosphamide plus other agents to
determine relationship between obesity and
– Clinical characteristics
– Clinical outcomes
– Clinical outcomes and breast cancer subtype
• ER/PgR-positive, HER2-negative disease
• HER2-positive disease
• Triple-negative disease
ECOG Trials Included in
Analysis
E1199
E5188
E3189
Population
• Node positive
• High-risk node
negative
• ER positive
• Node positive
• Premenopausal
• ER negative
• PgR negative
• Node positive
Chemotherapy
Cyclophosphamide,
doxorubicin, taxane
Cyclophosphamide,
doxorubicin,
fluorouracil
Cyclophosphamide,
doxorubicin,
fluorouracil vs
16-wk regimen
Endocrine
therapy
Tamoxifen ±
aromatase inhibitor
None vs goserelin
vs goserelin +
tamoxifen
None
3484
1502
613
Patients with
BMI data, n
Obesity and Outcomes in
Subgroup Analysis of E1199
E1199
Subgroup
DFS
HR (95%
P
CI)
Value
OS
HR (95%
CI)
P
Value
ER and/or PgR
positive, HER2
negative
1.23 (1.02-1.49)
.035
1.46 (1.15-1.85)
.002
ER, PgR, HER2
negative (n = 708)
1.01 (0.77-1.33)
.93
1.05 (0.77-1.43)
.75
HER2 positive
(n = 661)
1.07 (0.77-1.47)
.70
0.89 (0.60-1.31)
.55
Sparano J, et al. SABCS 2010. Abstract S2-1.
Validation by Analysis of Trial
Data From E5188 and E3189
Trial
DFS
HR (95%
P
CI)
Value
OS
HR (95%
CI)
P
Value
E5188 (ER/PgR
positive, HER2
negative)
1.41 (1.19-1.67)
< .0001
1.51 (1.24-1.83)
< .0001
E3189 (ER negative)
0.90 (0.70-1.16)
.41
0.83 (0.63-1.09)
.18
Sparano J, et al. SABCS 2010. Abstract S2-1.
Nutritional support in patients with
cancer
• Ginger
• Vitamin E effects on chemotherapy
Supportive care for those with
cancer
• Ginger for chemotherapy-related nausea in cancer patients: A
URCC CCOP randomized, double-blind, placebo-controlled clinical
trial of 644 cancer patients. J Clin Oncol 27:15s, 2009 (suppl; abstr
9511)
• Patients were randomized into four arms:
– 1) placebo,
– 2) 0.5g ginger,
– 3) 1.0g ginger, or
– 4) 1.5g ginger
• All doses of ginger significantly reduced nausea (p=0.003)
compared to placebo.
Vitamin E Inhibits Cisplatin-Induced
Apoptosis in MCF-7 Breast Cancer Cells.
% Apoptosis +
6Antioxidant
reduces
efficacy of
cisplatin
4**
2*
0Control
E
CP
CP+E
Salganik, et al. Carcinogenesis 21: 909, 2000.
American Cancer Society (ACS)
Recommendations for Individual Choices
http://caonline.amcancersoc.org/cgi/content/full/56/5/310
Maintain a healthy weight throughout life.
•Balance caloric intake with physical activity.
•Avoid excessive weight gain throughout the life cycle.
•Achieve and maintain a healthy weight if currently overweight or obese.
Adopt a physically active lifestyle.
•Adults: engage in at least 30 minutes of moderate to vigorous physical activity,
above usual activities, on 5 or more days of the week. Forty-five to 60 minutes of
intentional physical activity are preferable.
•Children and adolescents: engage in at least 60 minutes per day of moderate to
vigorous physical activity at least 5 days per week.
CA Cancer J Clin 2006; 56:254-281
American Cancer Society (ACS)
Recommendations for Individual Choices
Consume a healthy diet, with an emphasis on plant sources.
•Choose foods and beverages in amounts that help achieve and maintain a
healthy weight.
•Eat five or more servings of a variety of vegetables and fruits each day.
•Choose whole grains in preference to processed (refined) grains.
•Limit consumption of processed and red meats
If you drink alcoholic beverages, limit consumption.
•Drink no more than one drink per day for women or two per day for men.
CA Cancer J Clin 2006; 56:254-281
What Counts as a Serving?
Fruits
•
1 medium apple, banana, orange
•
1/2 cup of chopped, cooked, orcanned fruit
•
1/2 cup of 100% fruit juice
•
1 cup of raw leafy vegetables
•
1/2 cup of other cooked or raw vegetables, chopped
•
1/2 cup of 100% vegetable juice
•
1 slice bread
•
1 ounce ready-to-eat cereal
•
1/2 cup of cooked cereal, rice, pasta
Vegetables
Grains
What Counts as a Serving?
Beans and nuts
•
1/2 cup cooked dry beans
•
2 tablespoons peanut butter
•
1/3 cup nuts
•
1 cup milk or yogurt
•
1 1/2 ounces of natural cheese
•
2 ounces processed cheese
•
1 egg
Dairy foods and eggs
Meats
2–3 ounces of cooked lean meat, poultry, fish
Conclusions
• Inconsistencies in results of nutritional studies
– Observational studies
• Imprecise diet recall
• Confounding cancer risk factors
– Randomized studies
•
•
•
•
Poor adherence to dietary intervention
Insufficient follow up time
Wrong dose or form of nutrient
Study population may be replete with in nutrient studied
• One consistent finding is that excess calories
from any source leads to weight gain and
increased risk of multiple cancers
Conclusions by tumor type:
Breast Cancer
• Decreased risk
– Low fat diet may decrease risk
– Low fat dairy, calcium, Vit D (in premenopausal)
– Folic acid may decrease risk
• No difference
–
–
–
–
Red meat
Dietary fat
Fruits and Vegetables
Vitamin D and Calcium (in postmenopausal)
• Increased Risk
– Alcohol (2 or more drinks)
Conclusions by Tumor Type:
Prostate Cancer
• Increased risk
– large amounts of alpha-linoleic acid and low amounts
of linoleic acid increase risk of nonaggresive cancers
– Calcium?
• No difference
– Selenium
– Vitamin E
• Decreased risk
– Soy milk?
Conclusions by tumor type:
Colon cancer
• Decreased Risk
– Fish (men and women)
– Chicken without skin (women)
– Calcium and Dairy (men and women)Red meat
increases risk in men and women
• No difference
– Fiber
• Increased Risk
–
–
–
–
Red meat (men and women)
Processed meat
Liver
High glycemic load (men and women)
Conclusions by tumor type:
• Ovarian cancer
– Dairy may increase risk??
• “All cancers”
– Calcium + vit D
Just when I knew all of life’s answers,
They changed all the questions!!
Lifestyle changes
Caloric
Restriction in
Yeast causes
silencing of
genes and
extended life
span (Guarente
and Kenyon
Nature 2000;
408:255
Colon Cancer and Exercise
More is Not Always Better: Energy Intakes and
Expenditures Are Linked to Health!
Caffeine
Tea (Camellia sinensis)
Crushed tea leaves
Polyphenol oxidase
Oxidation,
Polymerization
HO
OH
Green Tea
30-40% Catechins
3-6% Caffeine
O
HO
R1
~310 mg polyphenols
per 6 ounces
OR 2
OH
Yang CS. Personal Communication
Black Tea
3-10% Catechins
2-6% Theaflavins
> 20% Thearubigens
3-6% Caffeine
~340 mg polyphenols
per 6 ounces
Tea and Cancer Prevention
Liver
Skin
Camellia Sinensis
Colon
Oral
Esophagus
Prostate
Stomach
Yang CS. Personal Communication
Mammary
Lung
Influence of Caffeine on Bone Mass May Depend on Genes
6
< 300 mg
Caffeine
> 300 mg
0
-6
-12
TT
Tt
tt
TT
Tt
Vitamin D Receptor Genotype
Rapuri et al. Am J Clin Nutr 2001 Nov;74(5):694-700
tt
Prospective cohort study with 41,837
women age 55 to 69, examined 127
food items. “The strongest
association in the present study was
that for garlic consumption, with an
approximate 50% lesser risk
associated with high consumption.”
Steinmetz et al. Amer. J. Epidemiology
139:1, 1994
Recent meta-analysis of Data from
11 trials concluded The randomeffects relative risk (RR) estimate
for raw and cooked garlic and
colorectal cancer was 0.69 and for
stomach was 0.53.
Fleischauer, et al. Amer JClin Nutr
72, 1047, 2000.
Linking diet, religion and cancer
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No.
18S (June 20 Supplement), 2007: 21172
• This study was done to see cancer incidence in children of Jain
religion as compared to other religions at a single centre.
– Jain religion does not consume garlic and onion due to religious belief.
• retrospective analysis of consecutive children less than 16 years of
age diagnosed with cancer at Sir Ganga Ram Hospital from January
2005 to January 2007.
• Incidence of cancer in children of different religions is similar to that
of proportions of population of different religions in Delhi except for
Jain religion where incidence of cancer is 6 times higher despite
lesser number children in 0-6 year in this population as compared to
other religions .
– Major difference is the diet lacking in onion and garlic .
– Other reason could be increased literacy levels in Jain community .
– “This link between diet ,religion and cancer in Jain population needs to
be studied in a larger muticenteric setting as it has implications for the
whole world.”
Selenium & Skin Cancer Prevention Trial
Phase III trial with 1,312 skin cancer subjects
Se (200 mg) as Brewers Yeast vs. Placebo, follow-up 6.4 yrs
Selenium Placebo RR
Skin Cancer
Squamous cell
Basal cell
Cancer (- Skin)
Lung
Prostate
Colorectal
Breast
97% CI
218
377
190
350
1.14
1.10
0.93-1.39
0.95-1.28
17
13
8
9
31
35
19
3
0.54
0.37
0.42
2.88
0.30-0.98
0.18-0.71
0.18-0.95
0.72-16.5
All Sites (- Skin)
77
119
Clark et al. JAMA 276: 1957, 1996.
0.63
0.47-0.85
Effects of Microwave Heating of Garlic
on Total DMBA-Induced DNA Adducts
DNA Adducts
(nmol Adducts/mol DNA)
1000
30 seconds
a
a
750
500
b
b
250
0
Control
Peel/
Crushed
Microwave/ Peel/
Crushed
Song and Milner J Nutr 1999;129:657-61
60 seconds
How Should We Consume Bioactive Food Components?
MARKET STAGE
BROCCOLI
3-DAY SPROUTS
3 grams
FREEZE-DRIED
SPROUT EXTRACT
150 grams
150 mg
All preparations contain the same quantity of detoxification enzyme
inducer activity, (Glutathione S-transferase and Quinone Reductase)