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

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

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

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

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

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.

PBDEsPolybrominated diphenyl ethers

Mandated Flame retardant

Used in upholstered furniture, foam mattress and cushions

Associated with disruption of thyroid function, slowed brain development, cancer

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

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

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.

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

Tips for the Home

Baking soda will clean sinks, tubs and toilets

Vinegar in a pump-spray bottle cleans mirrors, windows and chrome

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

Tips for the Home

Hydrogen peroxide – a better choice than bleach – breaks down to hydrogen and water

Bleaches made from hydrogen peroxide now available

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

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

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)

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

Cancer, Diet , Causes

Inflammation/Mediators

Oxidative Overload

Glycemic Overload

Detoxification

ALPHA-LIPOIC ACID

Antioxidant that helps reduce free radicals Improves insulin sensitivity, reduces

insulin resistanceAppears to improve glucose transport Dosage: 200-800mg daily

ANGIOPREVENTIVE COMPOUNDS

ANGIOPREVENTIVE COMPOUNDS

Araldi EM et al. Curr Cancer Drug Targets. 2008, 8(2):146-55

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

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

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”

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)

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

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)

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

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.

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.

For More Information www.

DrGaynor.comGaynorWellness.comDrKathrynCollins.comEnvironmentalHealthTrust.org