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THE BIOLOGY and ENVIRONMENTAL EPIGENETICS OF CANCER

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 Advisor Environmental Health Trust.

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THE BIOLOGY and ENVIRONMENTAL EPIGENETICS OF CANCER

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  1. 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 Advisor Environmental Health Trust

  2. One in 3 Americans will hear the words “You have cancer” Cancer and Environment • 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

  3. 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

  4. 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

  5. Women have an 82% lifetime risk of breast or ovarian cancer Inherited Breast / Ovarian CancerBRCA1 or 2 MutationFuture of Predictive Genomics • 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

  6. 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.

  7. PBDEsPolybrominated diphenyl ethers • Mandated Flame retardant • Used in upholstered furniture, foam mattress and cushions • Associated with disruption of thyroid function, slowed brain development, cancer

  8. Ethers that are used as flame retardants PBDEs(polybrominated diphenyl ethers) • 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

  9. Endocrine disrupting chemicals used in plastics to make them softer Phthalates • 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

  10. Avoid microwaving with wraps which contain dangerous plasticizers Tips for the Home Tupperware, rubbermaid bowls are made from polyethylene are safer options • Avoid upholstered furniture or foam products that have been treated with PBDEs. None of Ikea’s upholstered furniture contains PBDEs.

  11. x • 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. Tips for the Home Bottom line – Never microwave in plastic or cover in plastic wrap. Use glass or ceramic containers instead

  12. Avoid dishwasher detergents with chlorine and phosphates that release volatile organic compounds as vaporized mist Tips for the Home Practice Safe Phone and Safe Tech Distance is your friend Avoid using phones with weak signals Do not keep phones next to the body Use wired rather than wireless when possible Use speakerphone or wired headsets Sleep in the dark & quiet

  13. Baking soda will clean sinks, tubs and toilets Tips for the Home • Vinegar in a pump-spray bottle cleans mirrors, windows and chrome

  14. + Tips for the Home • Vegetable oil with lemon juice is good furniture polish • Use non-chlorine bleach

  15. 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

  16. Tips for the Home • Hydrogen peroxide – a better choice than bleach – breaks down to hydrogen and water • Bleaches made from hydrogen peroxide now available

  17. 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

  18. Minimize dry cleaning which uses chlorinated chemicals Tips for the Home • 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 Contact Organic Trade Association for more info at www.ota.com • Look for solid wood products certified by the Forest Stewardship Council

  19. 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)

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

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

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

  23. ANGIOPREVENTIVE COMPOUNDS

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

  25. 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

  26. 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

  27. 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”

  28. 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)

  29. 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

  30. METFORMIN • From diabetes to cancer… via angioprevention? • • It received approval by the U.S. Food and Drug • Administration (FDA) for Type 2 diabetes in 1994. Metforminis an insulin-sensitizer that reduces blood sugar levels: it reduces hepatic glucose output and increases peripheral glucose metabolism • Cardiovascular benefit(UKPDS and PRESTO study)

  31. VEGETERIAN PROTEIN SOURCES

  32. 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.

  33. 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 riskscan 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.

  34. For More Information www. • DrGaynor.com • GaynorWellness.com • DrKathrynCollins.com • EnvironmentalHealthTrust.org

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