1. STRAGIC PLANNING IN CANCER PREVENTION
Mitchell Gaynor, MD
Founder and President,
Gaynor Integrative Oncology
(www.gaynoroncology.com)
Assistant Clinical Professor of Medicine,
Weill-Cornell Medical College

2. To waste, to destroy our natural resources, to
skin and exhaust the land instead of using it
so as to increase its usefulness, will result in
undermining in the days of our children the
very prosperity which we ought by right to
hand down to them amplified and developed.
— Theodore Roosevelt

3. Cancer, Diet , Causes
Inflammation/Mediators
Oxidative Overload
Glycemic Overload
Detoxification

4. EPIC : DIET AND CANCER
Preliminary results:May,2004
• The European Prospective Investigation into
Cancer and Nutrition (EPIC) :The study
registered 519, 978 participants between 1992
and 2000 in 10 European countries. Cancer
incidence and cause-specific mortality to be
f/u for several decades.
• “Diet is the second leading cause (25%) of
all cancers”

6. Cancer Incidence
 Americans had a 132% increase in
melanoma, the deadliest skin cancer
between 1979 - 1998
 In New York State – Rates of non-Hodgkin's
lymphoma increased 76% for males and 49%
for females between 1975 - 1994
 In the US, incidence of lymphoma
has tripled since 1950
 Cancer is the leading cause of disease-related deaths in
children under the age of 15 and about one-third of
childhood cancers are leukemia

7. PBDEs
(polychlorinated biphenyl ethers)
 Ethers that are used as flame retardants
 Levels in harbor seals increased 100 fold
between 1989 and 1998
 Levels in human tissue in US were 10-40 times as
high as levels reported in earlier Swedish study
 Levels of PBDEs are now doubling every 5
years
San Francisco Bay Area – Breast tissue samples of women
showed highest levels in the world, up to 25 x greater than
European samples
Petreas, Myrto et.al. Env. Health Perspective, Vol 3, No. 9, July 2003

8. Solvents
 Chlorox (chlorine bleach), Freon (CFC) are examples of the
30,000 branded solvents available to households and
industry
 Uses: thinning paint, glues, washing electronics, dry
cleaning fabrics
 Most used trichloroethylene and methylene chloride
 1.5 billion pounds produced yearly in US
 Only 1% are reused or recycled
 94% released into environment – mostly air
 Many tied to cancer, birth defects, liver and
kidney damage

9. Bisphenol A
• ubiquitous polymer found in many everyday products that we use.
• also found in breast milk, placental tissue, fetuses
• Potential neurotoxicity due to pre-and perinatal exposure to BPA.
• lactating rats exposed to low levels bisphenol A (BPA) had offspring with a higher risk of developing
mammary cancers (Jenkins S, Raghuraman N, Eltoum I, Carpenter M, Russo J, Lamartiniere CA. Oral exposure to bisphenol A increases
dimethylbenzanthracene-induced mammary cancer in rats. Environmental Health Perspectives. 2009;117(6):910.
• A single exposure of BPA in mice during brain development disrupts spontaneous behavior and
cognitive function (Viberg H, Fredriksson A, Buratovic S, Eriksson P. Dose-dependent behavioral disturbances after a single neonatal Bisphenol A dose.
Toxicology. 2011.
BPA is found in paper and paper products such as newspapers, napkins, printer paper, toilet
paper, and receipts
Study evaluated over 200 paper samples from 15 different sources of paper products and reported
that BPA levels in paper and paper products were 100 to 1 million times greater than the amounts
detected in canned and packaged food products Liao C, Kannan K. Widespread Occurrence of Bisphenol A in Paper and Paper
Products: Implications for Human Exposure. Environmental Science & Technology. 2011/11/01 2011;45(21):9372-9379.
• Most absorb only a fraction of BPA through skin than from foods and beverages
• Amounts of BPA may be significantly higher for cashiers or printers (contact with more with BPA-
contaminated products)

10. What Are the Major Concerns When a
Toxic Disaster Happens
• What You Can Do to Protect Your Community
• Water, air, and soil are contaminated
• PCBs become dioxins and furans when incinerated, which means there’s
an increased risk of developing cancer
• Fetuses and children exposed to dioxins and furans are at risk for learning
disabilities and developmental disorders (e.g., ADHD and autism)
• Find and join your local environmental organization to stay informed
companies that handle toxic chemicals and wastes in your area
• Elect government officials in your community who have acted in support
of environmental protection
• Start a petition, hold community board meetings, call on local officials to
raise awareness in your community

11. DETOXIFYING ENZYMES and BREAST
CANCER
• JOHNS HOPKINS UNIVERSITY STUDY
– Compared genetic detoxifying enzyme ability of
110 patients with breast cancer vs. 113 controls
– Abnormal glutathione-S-transferase genes causing
decreased enzyme activity resulted in a fourfold
increased risk of breast cancer
(Helzlsouer, K. et al., J. Nat. Can. Inst. 1998)

12. CT Scan Hazards
• Researchers in Great Britain
• Evaluated the records of patients with any cancer
diagnosis.
• Those younger than 22 y.o. -correlation between
leukemia and brain tumors with radiation dose
from CT scans.
• dose of 50mGy or 60 mGy (mGy is a measure of
absorbed radiation dose) associated with 3X risk
developing leukemia or brain cancer.
• Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in childhood
and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. The
Lancet. 2012;380(9840):499-505.

13. OBESITY VS. DETOXIFICATION
•Fat production or fatty acid synthesis depletes
stores of NADPH, which is the body’s ultimate
reducing (antioxidant) agent.
•NADPH stores are required for the
regeneration of antioxidants (ARE) and
glutathione.

14. Hyperglycemia and
Cancer Mortality
Elevated fasting serum glucose levels
were associated with a 27% increase in
cancer mortality among men and a 31%
increase among women.
JAMA January 12, 2005 - Vol 293, No 2

15. NEJM Twin Study
 Identical twins developed same disease
only 10% of the time
 Both develop either breast, colon
or prostate cancer 14 – 30% of
the time
New England Journal of Medicine, 2000

16. Cancer-causing cellular changes
How it Leads to Cancer Development
• DNA damage
• DNA damage leads to ineffective cellular replication and uninhibited cellular proliferation is a
hallmark of cancer cells.
• Inflammation
• Chronic inflammation --associated with pro-inflammatory molecules (e.g. cytokines) that
damages tissues --lead to interrupted communication between cells that prevent normal cell-
to-cell interactions.
• Loss of Apoptosis - cells grow uncontrollably
• Invasiveness of cancerous tissue into healthy tissues through the use of tendrils
• Abnormal Angiogenesis
• Blood vessels supply normal tissues with nutrients, and cancer tissue also need
vascularization in order to survive and grow. Angiogenesis is the process in which new blood
vessels are formed, and in cancer cells these vessels form spontaneously to aid in the growth
of tumors.
• Metastasis
• Spread to other tissues in a process called metastasis, which is a defining characteristic of
malignancy.

17. Omega 3 and Barret’s
• Can an omega-3 fatty acid fish oil supplement increase tissue levels
in humans? Can the supplements actually suppress the
inflammatory COX-2 enzyme in humans?
• Patients with Barrett’s esophagus.
• Half of the patients were given 1500 mg of the omega-3 (EPA)
supplement, and the other half were not
• EPA-treated group had higher omega-3 fatty acid in their cells, and
the COX-2 protein was significantly decreased in the tissues of the
omega-3 supplemented group.
•
• Mehta SP, Boddy AP, Cook J, et al. Effect of n–3 polyunsaturated
fatty acids on Barrett's epithelium in the human lower esophagus.
The American Journal of Clinical Nutrition. 2008;87(4):949-956.

18. Metformin
• Shown to reduce the risk of breast and colorectal
cancers in type II diabetics.
• Why are researchers interested in metformin?
• To target (activate) AMPK, which is an enzyme that
promotes the uptake of glucose by muscle tissue.
• Also plays vital role in cancer prevention because an
enzyme called LKB1 (a tumor suppressor) is increased
by activation of AMPK.
• Diego E-P. Metformin May Lower Cancer Risk in People with Type 2 Diabetes. 2012;
http://www.sciencenewsline.com/articles/2012062523160029.html. Accessed July 18, 2012.
Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of
cancer in diabetic patients. Bmj. 2005;330(7503):1304-1305.

21. Broccoli and Prostate Cancer
• Volunteers were randomly assigned to either a broccoli-rich or a pea-rich diet.
• After six months
• no differences in gene expression between glutathione S-transferase mu 1 (GSTM1) positive
and null individuals on the pea-rich diet but significant differences between GSTM1
genotypes on the broccoli-rich diet, associated with transforming growth factor beta 1
(TGFβ1) and epidermal growth factor (EGF) signalling pathways.
• Comparison of biopsies obtained pre and post intervention revealed more changes in gene
expression occurred in individuals on a broccoli-rich diet than in those on a pea-rich diet.
• men on the broccoli diet had additional changes to mRNA processing, and TGFβ1, EGF and
insulin signalling.
• sulforaphane chemically interacts with TGFβ1, EGF and insulin peptides to form thioureas
• This study provides, for the first time, experimental evidence obtained in humans to support
observational studies that diets rich in cruciferous vegetables may reduce the risk of prostate
cancer and other chronic disease.
• Traka M, Gasper AV, Melchini A, et al. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling
pathways in the prostate. PLoS ONE. 2008;3(7):e2568.

22. Green Tea and Prostate Cancer
• Bertuzzi,S AACR 2005(abstract)
• 30 men with high grade PIN
• Randomized Control vs 600 mg/d green tea catechins
• Bx done at 0 and 12 mo
• 9 cases prostate CA control and 1 in Rx group at 1
year
• The 30% incidence at 1 year is c/w literature
• No adverse effects in Rx group

23. LIFESTYLE CHANGE-A NEW PROSTATE
CANCER RX ?
• 93 men with biopsy proven prostate CA
• Gleason’s score< 7
• All elected to forego conventional RX
• Randomized:
• Vegan diet, exercise, yoga/meditation vs.
control group
• After 1 year PSA decreased in LS group but
increase in control (J.Urol)2005.174(3)

24. Broccoli-prostate cancer prevention.
Ecogenetic Implications
• Volunteers were randomly assigned to either a
broccoli-rich or a pea-rich diet.
• given broccoli or peas in addition to their normal
diet for over a year.
• tissue samples obtained before during and after
the trial were examined.
• gene expression associated with a lower risk for
prostate cancer development was highly
associated with men who ate a broccoli rich diet.
• Traka M, Gasper AV, Melchini A, et al. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling
pathways in the prostate. PLoS ONE. 2008;3(7):e2568.

25. Mature analysis from Women’s
Intervention Study (WINS)
• Chlebowski,RT,et al SABCS 2006 Gen.
Session5:Abst 32 and JNCI Dec.2006
• 2400 women with early breast cancer at
UCLA: randomized prospective trial--low fat
(less than 20% cal. from fat) vs. control
• At 5.8 yrs; 22% fewer deaths- low fat diet
• Those with ER-/PR- there was a 66% reduction
in mortality

26. Fasting Insulin and Outcome in Early-Stage Breast
Cancer: Results of a Prospective Cohort Study
Purpose: Insulin, a member of a family of growth
factors that includes insulin-like growth factor (IGF)-I and
IGF-II, exerts mitogenic effects on normal and malignant
breast epithelial cells, acting via insulin and IGF-I receptors.
Because of this and because of its recognized association
with obesity, an adverse prognostic factor in breast
cancer, we examined the prognostic associations of insulin
in early-stage breast cancer.
J Clin Oncol 20(1):42-51, January 1, 2002

27. Fasting Insulin and Outcome in Early-Stage Breast
Cancer: Results of a Prospective Cohort Study
High levels of fasting insulin identify women
with poor outcomes in whom more effective
treatment strategies should be explored.
J Clin Oncol 20(1);42-51, January 1, 2002

28. VITAMIN D AND BREAST CANCER
Garland,Cedric et al.(UCSD) AACR 2006
Meta-analysis 1,760 women- 25-OH Vit. D levels
Multiple regression analysis: D3 level>52ng/ml assoc
with 50% lower risk breast CA compared with
levels<12 ng/ml.
Previous study (Prev Med 1990:19:614-22):
Demonstrated women living closer to the
equator, had significantly lower risk of breast cancer
death

29. Deficiency of Vitamin D, a Membrane Bound
Antioxidant, Linked to Poorer outcome in Breast
Cancer
• Vitamin D receptors found in breast cancer
cell nuclei
• Effects: slow cell growth, induces apoptosois
and differentiation
• 37.5% had levels < 50 (deficient), 38% 50-
71(insufficient), 24%>72(sufficient)
• Median f/u 11.6 years-Deficient patents 94%
>chance mets and 73%.chance of death than
patients with levels over 50.

30. Obesity /Survival /Ovarian Cancer
-Pavelka et al., Cancer (Published Online): 28 August 2006
●Evaluated association of of excess body weight on
ovarian cancer survival
●For patients with advanced stage disease, obesity was
independently associated with both shorter time to
recurrence and shorter overall survival. Findings suggest
adverse effect of excess body weight on tumor biology.

31. SOY ISOFLAVONES AND BREAST
PROLIFERATION
• Palomares,M San Antonio Breast Cancer Symposium(2005)
(Poster)
• 23 postmenopausal breast cancer (Stage I, II, DCIS) patients at
City of Hope National Medical Center
• Randomized:Isoflavone tab 100mg/d vs.placebo for 1 year
• Bx contralat. breast at 0, 6, and 12 mo:Ki67 index decreased
from baseline in Rx group by 3.1% vs.0.9% control (6 mo.) and
4.9% vs.4.1% (12 mo.) “Our findings suggest no negative
effects of soy and perhaps even a beneficial effect”

33. NF kappa-B Inhibitors
• Turmeric has been found to suppress the growth of many tumor cell lines
and causes regression of some precancerous lesions in humans.
• Nuclear factor-kappaB (NF-kB) proteins control inflammatory and
immune responses and are involved in cancer-related inflammation.
Studies show that curcumin blocks NF-kB.
• A major promoter of lung cancer is NF kappa B
• Transcription turned off by:
• turmeric (curcumin)
• kaempferol [found in teas and broccoli]
• procyanadins [grapes]
• sulforaphane [Brussels sprouts])
Bachmeier BE, Killian P, Pfeffer U, Nerlich AG. Novel aspects for the application of Curcumin in chemoprevention of various
cancers. Frontiers in bioscience (Scholar edition). 2010;2:697.
• Sikora E, Bielak-Zmijewska A, Mosieniak G, Piwocka K. The promise of slow down ageing may come from curcumin. Current
pharmaceutical design. 2010;16(7):884-892.

35. NF Kappa B and AP 1
•Transcription factors produced in excess by cancer cells
•Stimulate cancer cell proliferation
•Inhibit apoptosis
•Enhance inflammation
•Increased NF Kappa B activity in cancer cells is associated with poorer
prognosis, invasiveness and metastasis
(Nakshatri H, et al. Mol Cell Biol 1997 Jul; 17(7): 3629-39
Bours V, et al. Biochem Pharmacol 1994 Jan 13; 47(1): 145-9)

36. ALPHA-LIPOIC ACID
• Antioxidant that helps reduce free radicals
• Improves insulin sensitivity, reduces insulin
resistance
• Appears to improve glucose transport
• Dosage: 200-800mg daily

38. Honey
• Medicinal properties— antioxidant, anti-
inflammatory, antimicrobial, and antithrombotic
• Darker –colored honeys - more antioxidants than
lighter colored honeys
• Contains:
• Chrysin blocks the formation of estrogens from
androgens in the body.
• Galangin inhibits growth of breast cancer and
leukemic cells
• Mutation Research/Reviews in Mutation Research
• Volume 488, Issue 2, May 2001, Pages 135–150

39. Selenium
• Selenium supplementation (200 mcg/d) did
not affect primary endpoint of study, skin
cancer; but prostate cancer decreased by just
over 50% and colorectal cancer by
62%.(Clark, LC, et al, JAMA 1996; 276: 1957-
63)
• National and international correlations of
lower blood selenium with higher rates of
cancers.

40. Whole-grains and Cancer
● Fermented in the colon---1)Yields short-chain fatty
acids(SCFA) 2) SCFAs associated with reduced CRP 3)
provides immune protection by supporting GALT.
● Improve insulin and glucose responses.
● Bioflavonoids, phytates, lignans, stanols and sterols, B-
vitamins and minerals.
– Ajani et al., J Nutr. 2004 May;134(5):1181-5

41. FISH OIL
• Reduced risk of cancer
• EPA and DHA reduced the risk of further breast cancer events by 25%
among women with a history a breast cancer
• Consumption of 4000 milligrams of EPA supplements daily: reduces DNA
damage from UV light and increases the threshold in which skin burns due
to exposure of UV light by 36%--reduced the risk of skin cancer
• Risk of colon cancer –Subjects taking 2000 mg of EPA daily
• The consumption of 1000 mg of EPA and 1835 mg of DHA fish oil taken
before radical prostate surgery- reduction in cancer cell proliferation in
prostate tissue
• Patterson RE, Flatt SW, Newman VA, et al. Marine fatty acid intake is associated with Breast cancer prognosis. The Journal of nutrition.
2011;141(2):201-206.
• Rhodes LE, Shahbakhti H, Azurdia RM, et al. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in
humans. An assessment of early genotoxic markers. Carcinogenesis. 2003;24(5):919-925.
• Courtney E, Matthews S, Finlayson C, et al. Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic
mucosa in subjects with a history of colorectal adenomas. International journal of colorectal disease. 2007;22(7):765-776.
• Aronson WJ, Kobayashi N, Barnard RJ, et al. Phase II Prospective Randomized Trial of a Low-Fat Diet with Fish Oil Supplementation in Men
Undergoing Radical Prostatectomy. Cancer Prevention Research. 2011;4(12):2062-2071.

42. Curcumin-Induced Antiproliferative and
Proapoptotic Effects in Melanoma Cells Are
Associated with Suppression of Nuclear Factor KB
NF-kappaB plays a key role in cell survival and proliferation in human
melanoma
Evaluated NF-kappaB inhibition for melanoma treatment.
Curcumin, an agent with known, potent, NF-kappaB- inhibitory activity and
little toxicity in humans demonstrated antiproliferative and apoptosis
enhancing effects in melanoma cells.
Cancer 2005 Aug 15;104(4)879-90

43. Are we born with our genetic
destiny or can it be changed?
Agouti mice-- epigenetic changes
carried across generations
(Waterland and Jirtle, Mol.Cell.Biol.23:5293-
5300, 2003) (Env.Health Perspect 2006 April,114(4)
567-572)
Nutritional genomics vs.
toxicogenomics
Epigenetics :DNA methylation
and histone modification

44. ENDOCRINE DISRUPTORS
Vinclozalin, methoxychlor
Plastics(phthalates),pesticides
Reik,W et.al.2001Epigenetic reprogramming in mammalian development.
Science 293:1089-1093
Dolinoy et.al. Proc Natl. Acad Sci 104:13056-13061,2007

45. Epigenetic Effect of Targeted Nutrients
Folic Acid Leafy vegetables, sunflower seeds,
baker's yeast, liver
Methionine synthesis
Vitamin B12 Meat, liver, shellfish, milk Methionine synthesis
Vitamin B6 Meats, whole grain products,
vegetables, nuts
Methionine synthesis
SAM-e (SAM) Popular dietary supplement pill;
unstable in food
Enzymes transfer methyl groups from SAM directly to
the DNA
Choline Egg yolks, liver, soy, cooked beef,
chicken, veal and turkey
Methyl donor to SAM
Betaine Wheat, spinach, shellfish, and sugar
beets
Break down the toxic byproducts of SAM synthesis
Resveratrol Red wine Removes acetyl groups from histones, improving health
Genistein Soy, soy products Increased methylation, cancer prevention, unknown
mechanism
Sulforaphane Broccoli Increased histone acetylation turning on anti-cancer
genes
Butyrate A compound produced in the intestine
when dietary fiber is fermented
Increased histone acetylation turning on 'protective'
genes, increased lifespan (shown in the lab in flies)