Transcript Nutricao e o Cancro da Prostata

Nutricao e o Cancro da Prostata
XV Workshop de Urologia
Oncologica
J.Edson Pontes
KCI/WSU
World Cancer Research Fund
American Institute for Cancer Research
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Food, Nutrition, Physical Activity, and the Prevention of Cancer:
A Global Perspective
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Major Publication for Nutrition Recommendations Related to
Cancer
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http://www.dietandcancerreport.org/
500+ pages
November 2007
A Review of thousands of scientific articles
Authors state that these recommendations are intended for
cancer survivors as well
WCRF/AICR
Key Recommendations
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If you drink alcohol, limit to:
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≤ 2 drinks/day for men
≤ 1 drink/day for women
1 drink = 5 ounces of wine
1.5 ounces of hard liquor
12 ounces of beer
Dietary supplements (vitamin, minerals, other natural
supplements) are not generally practical for cancer
prevention
WCRF/AICR Key
Recommendations
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Consume “fast foods” sparingly, if at all
Limit salt intake
Avoid moldy grains and legumes (including peanuts)
Eat mostly foods of plant origin
Eat < 18 oz (~24 oz raw) of cooked red meat (beef, pork,
lamb) per week
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Be wary of portion size
Which One is a Healthy
Portion Size?
WCRF/AICR
Key Recommendations
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Be as lean as possible –
Keep body mass index (BMI) between 21 and 24 kg/m2
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Avoid increases in waist circumference
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Calculate BMI:
http://www.cdc.gov/healthyweight/assessing/bmi
Goal: < 31.5 inches – women
Goal: < 37 inches – men
Exercise Daily
Avoid sugary drinks (Coca-Cola, Lemonade)
Diet May Influence Genetic & Epigenetic Events
Associated with Several Cancer Processes
DNA
Repair
Carcinogen
Metabolism
Bioactive
Food
Components
Cell
Cycle
Hormonal
Regulation
Differentiation
Apoptosis
The Science is Difficult
MARKET BROCCOLI
3-DAY SPROUTS
3 grams
150 grams
FREEZE-DRIED
SPROUT EXTRACT
These preparations contain the same quantity of
detoxification enzyme inducer activity, (Glutathione
S-transferase and Quinone Reductase)
150 mg
Types of Bioactive Compounds May Vary
with New Varieties
Tomato Varieties
Diet-Based Interventions
THIS IS NOT
 General concept:
“COMPLEMENTARY”
OR
– Altering diet in prostate cancer patients may
possibly slow prostateMEDICINE!
cancer initiation and/or
“ALTERNATIVE”
progression
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Interventions:
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Change in diet
Supplements
Typical Well-educated PC Patient
Vegetables
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Pre-clinical evidence:
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Components of crucifers (isothiocyanates, indole 3carbinols) and tomatoes (carotenoids):
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Induce apoptosis of prostate cancer cells
Inhibit carcinogenesis
Promote expression of cytoprotective enzymes
Protect against oxidative DNA damage
Cancer Res, 67: 836, 2007.
Cancer Epidemiol Biomarkers Prev,10:949, 2001.
J Natl Cancer Inst, 93:1872, 2001.
Cruciferous Vegetables
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Broccoli (baby broccoli sprouts), brussel sprouts,
cauliflower, kale
Indole 3-carbinols
– in vivo dimeric derivative: 3, 3′-diindolylmethane
(DIM)
– Conversion of I3C into DIM during cooking
Epidemiological studies (PLCO, HPFS) show
protective effect
Cruciferous Vegetables
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Mechanisms in prostate cancer cells and animal models:
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inhibition of cell growth
induction of G1 cell-cycle arrest
Induction of apoptosis by upregulation of BAX, downregulation of
Bcl-2 and BCLXL
inactivation of Akt and NF-kB
anti-androgen
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DIM down-regulated PSA expression at the transcriptional levels
no androgen receptor (AR) agonist activity
LNCaP
C42B
Sarkar et al.
Androgen
Receptor
and
B-DIM
LNCaP
C42B
(AR-immuno-fluorescence)
Control
B-DIM
Sarkar et al.
SCID-Human Model of Prostate
Cancer Bone Metastasis
1 cm
Normal
PC3
LNCaP
Cher et al.
LUCaP 23.1
B-DIM and SCID-Human Model of Prostate
Cancer Bone Metastasis
Sarkar et al.
Tomatoes
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Putative active agent: lycopene
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Free radical scavenger
Induces apoptosis
Epidemiological studies inconsistent
Emerging consensus:
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Tomatoes moderately beneficial
Lycopene perhaps not
Processed tomatoes possibly even better than raw
Tomatoes and Prostate Cancer
Meta-analysis of Published Studies
Soy
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Phase II studies show promise for high soy
diets for biochemical recurrence
Studies are ongoing
• Urology 64: 510, 2004
• Prostate 59: 141, 2004
Soy Products
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Rich in isoflavones (genistein and daidzein) and
phytoestrogens
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Anti-oxidants
Inhibit tumor cell proliferation
Possible effect on telomerase
Estrogenic effects/alterations in androgen receptor
Decrease prostate cancer risk in large
epidemiological studies
Soy Intake and Cancer
17 of 26 animal studies reveal soy or
soybean isoflavones reduce tumor
development
19 of 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 isoflavonoids (Hsieh, et al. Cancer Res. 58:3833,
1998).
Soymilk Intake & Prostate
Cancer Risk
1.0
Relative Risk
0.9
0.8
0.3*
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<1
1
Daily Intake (servings)
Cancer Causes Control 9: 553, 1998
>1
Soy: Meta-Analysis of
Epidemiological Studies
30% Reduction in
Prostate Cancer Risk
Prostate Cancer Bone Metastasis:
Dietary Genistein (Soy),
Matrix Metalloproteinases
Michael L. Cher, Yiwei Li, Mingxin Che, Sunita Bhagat, Kerrie-Lynn Ellis,
Omer Kucuk, Daniel R. Doerge, Judith Abrams, and Fazlul H. Sarkar
Genistein
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Soy isoflavone
Cancer prevention (Asian Diet)
Pleiotropic anti-tumor effects
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Phytoestrogen, inhibitor of protein tyrosine
kinases, inhibit NF-κB and Akt activation
Inhibit cancer cell proliferation and invasion,
induce cancer cell apoptosis, inhibit tumor
angiogenesis
Proteases and the “Vicious Cycle”
Expansion
of tumor in
bone
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» Decreased osteoclast recruitment
» Decreased bone degradation
» Decreased growth of tumor in bone
MMP
Activity
Bone
matrix
turnover
MMP Inhibition – osteolytic tumors:
– Nemeth et al., JNCI, 2002.
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Winding et al., Clin Cancer Res, 2002.
Lee et al., Eur J Cancer, 2001.
Weber et al. Int J Oncol, 2002.
Dietary Genistein and Experimental PC3
Bone Metastasis
p0.0001
p=0.0003
control
prevention
Dietary Genistein and Experimental PC3
Bone Metastasis
control
MMP-9
(red color)
Prevention (genistein)
Soy and Bone Metastasis:
Summary
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Dietary genistein disrupts the MMP vicious cycle
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Decreased gene and protein expression of many MMPs including
MMP-9
Pleiotropic effects on various cell cycle pathways
Not due to estrogenic effects
Not due to direct anti-proliferative effect
Fish
(Omega-3 fatty acids)
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Decrease prostate cancer risk
in large epidemiological studies
Omega-3 polyunsaturated fatty
acids
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alter cyclooxygenase (COX-2)
pathways
Inhibit tumor growth
Induce apoptosis
Phase II biomarker studies
currently underway
Meat and Animal Products
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Increase prostate cancer risk in large epidemiological studies
Red meat
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Cooked meats contain various mutagens
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Heterocyclic amines when meat cooked at high temperature
Polycyclic aromatic hydrocarbons: fat drips on coals which then flame up
Risk may be higher for processed meats
Dietary fat
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Increases risk of aggressive cancer and recurrence after treatment
Weight loss > 11 lbs = 40% risk reduction in high-grade cancer
Grilling? Reduce Risk
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Choose lean cuts (i.e., not ribs or sausage)
Avoid nitrite-cured (hot dogs, bacon, ham)
Flip burgers often
Cook to at least 160°F, but not to well done
Use thin marinades, not thick sauces
Trim fat from red meat and skin from poultry
Avoid flame ups by using tongs, not forks
Remove charred areas
Marinate or cook meats in antioxidants
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vinegar, citrus juice, olive oil, cherries, vitamin E, garlic, rosemary, sage,
soy powder
Pre-cook in microwave and finish on grill
A Brief Word on Pomegranate Juice…
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Single trial of 46 patients
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Increased PSADT in patients with biochemical recurrence (that’s a
good thing)
Limited laboratory studies
No epidemiological studies
Pro-apoptotic, anti-proliferative, and anti-oxidant?
Summary
What to tell your patients
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Studies are ongoing—nothing definitive yet.
Heart healthy = Prostate healthy
There is little downside to making changes in
nutritional intake
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Vegetable intense diet
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Tomatoes
Broccoli
Soy
Fish
Decrease meat, fat, and animal product intake