THE BIOLOGY and ENVIRONMENTAL EPIGENETICS OF CANCER
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THE BIOLOGY and ENVIRONMENTAL EPIGENETICS OF CANCER
Mitchell Gaynor, MD
Founder and President, Gaynor Integrative Oncology
Assistant Clinical Professor of Medicine,Weill-Cornell Medical College
Scientific AdvisorEnvironmental Health Trust
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Cancer and Environment One in 3 Americans will hear
the words “You have cancer” More Americans are surviving
cancer – 9.8 million Americans in 2001 vs 3 million living with cancer in the early 1970s
Cancer rates are increasing in many categories:- In 2003 cancer cases in US increased 3.8%- Non-Hodgkin Lymphoma rates tripled since 1950’s- 1 in 7 women now develop breast cancer, compared to 1 in 22 in 1940
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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
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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
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Inherited Breast / Ovarian CancerBRCA1 or 2 Mutation
Future of Predictive Genomics Women have an 82% lifetime risk of breast or
ovarian cancer Risk has increased since 1940
Risk of breast cancer 24% if born before 1940 but 67% if born after 1940
Risk of ovarian cancer was twice as high for BRCA1 carriers and 23% higher for BRCA2 carriers if born after 1940
King et.al Science 24 October 2003 Vol.302 P 643-646
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Toxic Compounds: Present in Over 75%
of All Samples Tested by the EPA
Since 1976, the Environmental Protection Agency (EPA) has been measuring toxins from fatty tissue of both autopsies and patients undergoing elective surgery in the U.S.
20 toxic compounds, including OCDD (a dioxin), styrene,1,4-dichlorobenzene, xylene, toluene, DDE and PCBs were found in more than 75 percent of all samples.
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PBDEsPolybrominated diphenyl ethers
Mandated Flame retardant
Used in upholstered furniture, foam mattress and cushions
Associated with disruption of thyroid function, slowed brain development, cancer
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PBDEs(polybrominated diphenyl 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
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Phthalates Endocrine disrupting chemicals used in plastics
to make them softer Found in nail polish, soft plastic toys for
infants, solvents, flavorings, perfumes, skin moisturizers
PHP - common phthalate in hair sprays, cosmetics, shampoo
PHP linked to birth defects and reproductive impairment in animals
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Tupperware, rubbermaid bowls are made from polyethylene are safer options
Tips for the Home
Avoid microwaving with wraps which contain dangerous plasticizers
Avoid upholstered furniture or foam products that have been treated with PBDEs. None of Ikea’s upholstered furniture contains PBDEs.
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Tips for the Home
Heating plastic wrap with olive oil in a microwave results in concentration of xenoestrogens 500,000 times greater than the minimum amount of estrogen needed to induce cancer cells in a test tube.
Bottom line – Never microwave in plastic or cover in plastic wrap. Use glass or ceramic containers instead
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Tips for the Home
Avoid dishwasher detergents with chlorine and phosphates that release volatile organic compounds as vaporized mist
Practice Safe Phone and Safe TechDistance is your friendAvoid using phones with weak signalsDo not keep phones next to the bodyUse wired rather than wireless when possibleUse speakerphone or wired headsetsSleep in the dark & quiet
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Tips for the Home
Baking soda will clean sinks, tubs and toilets
Vinegar in a pump-spray bottle cleans mirrors, windows and chrome
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Tips for the Home
Vegetable oil with lemon juice is good furniture polish
Use non-chlorine bleach
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Tips for the Home
Chlorine bleach is potentially carcinogenic and toxic to lungs. Its byproducts that contaminate air : chloroform, trihalomethanes and chlorinated hydrocarbons
Other chemicals in chlorinated products act as xenoesrogens, thus increasing risk of breast cancer
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Tips for the Home
Hydrogen peroxide – a better choice than bleach – breaks down to hydrogen and water
Bleaches made from hydrogen peroxide now available
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Tips for the Home
Borax is safer laundry detergent
Use non-bleached coffee filters
Skip synthetic air fresheners – use all natural scented oils and candles
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Tips for the Home Minimize dry cleaning which
uses chlorinated chemicals
Hardwood plywood paneling and particle board used in shelving omit VOC’s either in wood itself or from resins and glues used to hold them together
Look for solid wood products certified by the Forest Stewardship Council
Contact Organic Trade Association for more info at www.ota.com
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DETOXIFYING ENZYMES and BREAST CANCER
JOHNS HOPKINS UNIVERSITY STUDYCompared 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)
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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
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Cancer, Diet , Causes
Inflammation/Mediators
Oxidative Overload
Glycemic Overload
Detoxification
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ALPHA-LIPOIC ACID
Antioxidant that helps reduce free radicals Improves insulin sensitivity, reduces
insulin resistanceAppears to improve glucose transport Dosage: 200-800mg daily
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ANGIOPREVENTIVE COMPOUNDS
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ANGIOPREVENTIVE COMPOUNDS
Araldi EM et al. Curr Cancer Drug Targets. 2008, 8(2):146-55
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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
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VITAMIN D AND BREAST CANCER
Garland,Cedric et al.(UCSD) AACR 2006Meta-analysis 1,760 women- 25-OH Vit. D levelsMultiple 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
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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”
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LIFESTYLE CHANGE-A NEW PROSTATE CANCER RX ?
93 men with biopsy proven prostate CAGleason’s score< 7All elected to forego conventional RXRandomized:Vegan diet, exercise, yoga/meditation vs.
control groupAfter 1 year PSA decreased in LS group
but increase in control (J.Urol)2005.174(3)
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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
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METFORMIN F
rom diabetes to cancer… via angioprevention?
• It received approval by the U.S. Food and Drug
Administration (FDA) for Type 2 diabetes in 1994.
Metformin is an insulin-sensitizer that reduces blood sugar levels: it reduces hepatic glucose output and increases peripheral glucose metabolism
Cardiovascular benefit(UKPDS and PRESTO study)
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VEGETERIAN PROTEIN SOURCES
Silken Tofu 3oz ¼ block 5 grams/protein
Block Tofu (in water) 3oz or 1/5 block 12 grams/protein
Tempeh 4oz (½ container) 12 grams/protein
Soy milk 8 ounces 10 grams/protein
Soy beans ½ cup 24 grams/protein
Legumes, beans, lentils ½ cup 6 grams/protein
Soy cheese 1 ounce 7 grams/protein
Nuts ¼ cup 5 grams/protein
Eggs 1 7 grams/protein
Yogurt 1cup 10-12 grams/protein
Cheese 1 ounce 7-10 grams/protein
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EXERCISE
Aerobic exercise has been shown to reduce insulin resistance by improving blood supply to the muscle, which allows for more glucose uptake into muscle tissue.
Exercise should be frequent and regular to be effective.
Exercise should involve all the major muscle groups for at least 20-30 minutes 4-5 days/week.
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We Cannot Wait for AbsolutesThe Precautionary Principle*We must act on facts and on the most accurate interpretation of them, using the best scientific information. That does not mean we must sit back until we have 100% evidence about everything. Where the state of the health of the people is at stake, the risks can be so high and the costs of corrective action so great, that prevention is better than cure. We must analyze the possible benefits and costs of action and inaction. Where there are significant risks of damage to the public health, we should be prepared to take action to diminish those risks even when the scientific knowledge is not conclusive, if the balance of likely costs and benefits justifies it.Source: Richard Horton, Editor-in-chief, Lancet. *Modified from a 1990 UK Department of the Environment definition. Lancet, Vol. 352. No. 9124, 5 July, 1998.
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For More Information www.
DrGaynor.comGaynorWellness.comDrKathrynCollins.comEnvironmentalHealthTrust.org