Epigenetics : keeping abreast: on breast health

1. Epigenetics: keeping abreast: on breast health By Kathleen Cole BSc in Nursing, Naturopath

2. The Fear of Breast cancer starts early

3. What is Epigenetics? • True genetic mutations account for only 5-10% cancers • Epigenetic research suggests that many cancers are not initially caused by mutations in the genes but by changes in how genes function: • Tumour suppressor genes silenced • Tumour promoter genes expressed • Cell division accelerates • Chromosomal instability

4. Epigenetic Terrain of cancer

5. Epigenetics • Both genetic and epigenetic changes impact on health and disease susceptibility through • Environment • Diet • Stress • Hormones • Cancer is a disease of the Genome relationship to Epigenome • A genome is the complete set of deoxyribonucleic acid, or DNA, in a cell. DNA carries the instructions for building all of the proteins that make each of us unique. • epigenome means "above" the genome. The epigenome consists of chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it and when to do it. The marks, which are not part of the DNA itself, can be passed on from cell to cell as cells divide, and from one generation to the next.

6. Epigenetic Mapping • Gene expression • DNA methylation • Chromatin modification • SNP- Single Nucleotide Polymorphisms-a code that reveals how we uniquely metabolize and detoxify certain environmental toxins and drugs- can explain why some therapies work better than others for individuals

7. What is methylation and why is it so important • In simple terms it is a process in which certain chemicals called ‘methyl groups’ are added to various constituents of proteins, DNA and other molecules.  These are needed to keep them functioning normally. • Methylation of certain parts of your DNA can switch off unnecessary genes and prevent abnormal DNA division.  This means that these abnormalities are not passed on to future generations of cells

8. Hypomethylation and cancer • Tumour cells are characterised by general DNA hypomethylation • Methylation of normal genes act as defensive mechanisms against cancer- an example is oncogenes (cancer genes), can be silenced and prevented from being read by being methylated • Hypomethylation causes breakdown of this defense mechanism and is implicated in tumourigenesis

9. DNA Methylation

10. Hypomethylation and tumourigenesis • Hypomethylation in malignant cells is one of the first epigenetic alterations in human cancer leading to genetic instability and further hypomethylation as cancer progresses. • Hypermethylation of CpG genes in promoter regions of tumour suppressor genes occurs as tumourigenesis progresses

11. What alters methylation and gene activation? • Detabilization of chromosomes- Aneuploidy- abnormal number of chromosomes- initiated through carcinogen damage • Inflammation • Diet and nutritional factors • Insulin resistance • Immune imbalance • Hormonal influences • Oxidative stress

12. Oxidative stress and shortened telomeres • Lifetime oxidative stress leads to chromosomal instability and shortened telomeres • Cells with high turnover rate are more vulnerable to cancer development- telomeres shorten with each division • One reason chronic inflammation increases cancer risk because inflamed tissue has a higher rate of division • Telomeres are specialized structures at the end of the chromosome that are involved in the replication and stability of DNA molecules.

14. Inflammation • Inflammation from low grade infection, or autoimmune conditions can increase risk of developing breast cancer as well as driving its progression through: • Mitosis- division of cells • Metastasis- spreading of cancer to other tissue • Angiogenesis- growth of new blood vessels to feed the tumours

15. Cancer as an unhealed wound • Cancer is an unhealed wound that creates a vicious cycle of prolonged inflammation • Cancer cells stimulate fibroblasts and immune cells to secrete chemicals that are normally only present for short periods of time during wound healing. • Tissue specific fibroblasts can promote breast cancer progression by increasing production of I-L6, estradiol and other signalling molecules

16. Lowering Fibroblast production of IL-6 • Natural substances that can lower IL-6 production: • EGCG- green tea • luteolin • Apigenin • Dietary sources: celery, spinach, fennel, parsley, chives, thyme, hot peppers

17. Metastasis and inflammation • Cancer cells that favour bone metastasis secrete large amounts of I-L6, which helps in bone invasion and metastatic lesions. • I-L6 produced by cancer cells initiates downstream signalling that can lead to bone destruction • I-L6 signalling results in stimulation of osteoclast differentiation resulting in bone destruction

18. High levels of IL-6 increase tumour proliferation and survival

19. NF-kB- connection between inflammation and cancer • NF-kB regulates expression of genes involved in tumourigenesis • NF-kB is a mediator of chronic inflammation • NF-kB is activated in various stem cells • NF-kB can increase IL-6 production • Downregulation of NF-kB expression may suppress the pro-inflammatory and growth promoting factors

20. Anti-inflammatory diet • low glycemic- “sugar feeds cancer”- recent research has shown low GI diets can reduce growth of cancer cells • Balance of Essential fatty acids in favour omega 3 • Foods high in flavonoids and anti-oxidants- fruits and vegetables aromatic spices- turmeric, chilli, ginger • High Fibre-quinoa, oats, fruit & vegetables, flaxseed • Alkaline diet- cancer cells thrive in an acidic environment

21. Flavonoids and other anti-inflammatory nutrients downregulate NF-kB expression • Green Tea -inhibits some of these tumour macrophages . • Vitamin C and Carotenoids- fresh fruit & veges • Tumeric- curcurmin • Quercetin and bromelain- found in onions (red), pineapple, apples, broccali • Omega 3 fish oil and vitamin D • A study demonstrated that regular use of fish oil supplements, which contain high levels of the omega-3 fatty acids EPA and DHA, was linked with a 32% reduced risk of breast cancer. • http://foodforbreastcancer.com/news/fish-oil-supplements-reduce-risk-of-ductal-breast-cancer

23. Breast care starts with a balanced immune system, healthy liver & gut function, hormonal & emotional balance- all of these epigenetic factors can influence your risk of breast cancer • Your immune system and specifically your Natural Killer cells regularly deal with any abnormal cellular growth • It is when your immune system becomes imbalanced that abnormal cell growth is allowed to progress to latter stages.

24. TH1 and TH2 Immunity • Immune balance is controlled by the balance of cytokines produced by TH1 or TH2 subsets • TH1 cells produce IL-12 and IFN-y and play a role in cellular immunity- which produces T lymphocytes, NK cells and cytokines in response to antigens • TH2 cells produce IL-4, IL-5 and IL-6 and involved in humoral immunity which produces antibodies in response to antigen- mediated by B lymphocytes

25. Cancer is generally TH2 Dominant • Factors that induce TH2 and suppress cellular mediated immunity are the usual suspects: • Environmental toxins • Chronic stress- increased cortisol, poor sleep • Dysbiosis- altered bowel flora- TH3 defense • Insulin resistance- high sugar diet • Trans fats • Thoughts and Emotions have a direct effect on the immune system through their effect on the Hypothalamus, Adrenal & sympathetic nervous system

26. Emotions associated with breast cancer • Not feeling appreciated • Feeling unheard • Worry & negativity • Always putting others first • Solution: • Practice Appreciation- research through Heart Math technology shows this emotion reduces anxiety and negativity.

27. Balancing immunity and upregulating TH1with Melatonin • Melatonin is: • Antioxidant and cytoprotective • Immunmodulator- increases T cell activity • Lowers oestrogen production • Decreases angiogenic endothelin-1 and increases p53 expression • Stimulates apoptosis • Alters adhesion molecule expresson- reduces invasiveness

28. Immunmodulators to balance TH1 and TH2 • Astragalus • Carotenoids- lutein, D salina, astaxanthin • Maitake, reishi, shitake, coriolus mushrooms • ECGC

29. Light Toxicity and melatonin • New Research Shows Artificial Light at Night Stimulates Breast Cancer Growth • Results from a new study show that night-time exposure to artificial light stimulated the growth of human breast tumors by suppressing the levels of a key hormone called melatonin. The study also showed that extended periods of nighttime darkness greatly slowed the growth of these tumors. • The results are published in the December 1, 2005 issue of the scientific journal Cancer Research.

30. Oestrogen metabolism • Research over the past decade shows the development of breast cancer appears to be related to how the body breaks down oestrogen once it has performed its essential duties. • There are 3 main oestrogen metabolites- 2OH is the protective form, 16 and 4 are toxic. The ratio of these is important to protect against the oestrogen stimulation of breast cells.

31. Estrogen Metabolism

32. Keeping a healthy oestrogen metabolism ratio Consume a high plant based diet preferably organic • Eat cruciferous/brassica vegetables- broccali, brussel sprouts, kale- eliminates carcinogens & reduces cancer development • Genistein-soy • Lignans- flaxseed, lentils, alfalfa sprouts • Calcium d glucorateinhibits enzyme beta-glucaronidase associated with increased breast cancer risk • Found in apples, broccali, cabbage, brussel sprouts • Liver detoxification, and healthy bowel flora Researchfocuses on the anti-cancer activity of one of these compounds, called sulforaphane"It has already been shown to reduce the incidence and rate of chemically induced mammary tumors in animals. It inhibits the growth of cultured human breast cancer cells, leading to cell death."

33. Studies on nutrition & cancer risk • A UK women’s Cohort study found a fibre rich diet containing 30g of fibre per day was associated with 52% reduction in the development of breast cancer in pre-menopausal women compared with diet less than 20g per day. Another study found that women who ate few • vegetables had an incidence of breast cancer that was about 25% higher than those who consumed more vegetables.

34. FIBROCYSTIC BREAST DISEASE Most breast changes are not due to breast cancer and are often related to hormonal changes such as in FBD- although a benign condition, is nevertheless an indication of a hormone imbalance. Contributing causes: • synthetic hormones • xenoestrogens in the environment • lack of fibre and constipation • caffeine • Lack of exercise • High saturated fats & excess animal protein • Relative oestrogen dominance and progesterone deficiency • These are all risk factors for breast cancer

35. What are the known risk factors for Breast Cancer/disease • Increasing age- breast cancer occurs more frequently in women between 50 and 65. • Family history- increased risk if a family member has had breast or ovarian cancer- only 5-10% breast cancers are hereditary • Childbearing- having your first child after 35 or never having children • Menstruation and menopause- early menses and late menopause- higher oestrogen exposure

36. Risk factors con’t • Hormone therapy- HRT- studies have shown there is some increased risk • Obesity- weight gain in pregnancy that is not lost after birth and weight gain after menopause especially around the waist • Body fatness directly affects levels of circulating hormones such as insulin ,insulin growth factors and oestrogens. • Insulin resistance • Acidic environment

37. Risk factors Con’t • Alcohol-Study Shows Moderate Alcohol Consumption Associated with Increased Cancer RiskSmoking -increases risk and survival • Poor nutrition- high saturated fats/trans fats,low levels of antioxidants and B vitamins including folate, low fibre, high sugar. Lack of exercise • Environmental exposure to xenoestrogens • Radiation exposure (younger you are when exposed greater risk)

38. ENVIRONMENTAL RISK • Studies of women who migrate from areas of low risk to areas of high risk of breast cancer assume same rate in host country within 1 or 2 generations. This would indicate environmental factors as well as dietary changes are important in the progression of breast cancer. Women with high agricultural organochlorines in their blood are 4 to 10X more likely to develop breast cancer than those with lower levels • New Zealand Pesticides Campaign coordinator Meriel Watts wrote: Of particular concern to women is the increasing number of reports linking breast cancer to organochlorine pesticides”

39. Xenoestrogens • Avoid Xenoestrogen Substances • Xenoestrogens are chemical compounds from environmental pollutants that mimic estrogen and attach to estrogen receptor sites,causing endocrine disruption • Xenoestrogen Sources :- Commercial meat and dairy products - Pesticide residues - Soft plastics - Laundry detergents and household cleaning products - Heavy metals like lead and mercury • Synthetic cosmetics & underarm deoderent • Counteracting Xenoestrogen Substances - Consume more foods like broccoli, brussel sprouts, cabbage, kale garlic, onions

40. CELLULAR DETOXIFICATION DETOXIFICATION = • HEALTHY CELLULAR FUNCTION • IMMUNE SYSTEM REPAIR • METABOLIC FUNCTION NORMALIZED • ACID-ALKALINE BALANCE RESTORED • ELIMINATION PATHWAYS RE-ACTIVATED • ESSENTIAL FOR CHRONIC DISEASE PREVENTION INCLUDING CANCER

41. Oxygenation and alkalization • The science of acid cells and acid bodies • Dr. Otto Warburg was awarded the Nobel Prize in 1931 for the discovery that, unlike healthy cells in the Human body, cancer cells • do not "breathe" oxygen. Cancer cells are anaerobic, in other words they function with no oxygen present. • Deep breathing, exercise and an alkaline diet ( see 80/20 diet) will create a cancer free environment.

42. Insulin Resistance/ Metabolic Syndrome • Women with insulin resistance have a higher risk of breast cancer • Insulin resistance occurs when cells no longer respond to insulin and glucose cannot enter the cells so blood glucose rises & fat is stored. • Main cause is a diet high in sugar and refined carbohydrates, obesity, sedentary lifestyle • Metabolic syndrome increases breast cancer risk among postmenopausal women • http://foodforbreastcancer.com/news/metabolic-syndrome-increases-breast-cancer-risk-among-postmenopausal-women

43. HYDRATION • Drink 1.5 litres of pure water a day- 90% of cells are made up of water- this is important for healthy cells- eliminating toxins and absorbing nutrients.

44. BURN THE BRA • Singer and Grismaijer then studied 4,500 women in five cities across the US about bra wearing habits. Published findings in book “Dressed to Kill” • 3 out of 4 women who wore their bras 24 hours per day developed breast cancer • 1 out of 7 women who wore bras more than 12 hour per day but not to bed. • 1 out of 152 women who wore their bras less than 12 hours per day. . 1 out of 168 women who wore bras rarely or never.

45. HERE COMES THE SUN • High levels of vitamin D translated to a 50 percent lower risk of breast cancer, one study found. • A second study, by Canadian researchers, found that women who spent time outdoors or got a lot of vitamin D from their diets or supplements — especially as teens — were 25 percent to 45 percent less likely to develop breast cancer than women with less of the nutrient.

46. Thyroid and iodine link • When thyroid function is low, estrogens are unable to activate an estrogen binding protein-(SHBG) in the liver. • Unbound oestrogen can then stimulate growth of tissues in the breast and uterus • Iodine is required for thyroid production, eliminating breast cysts and reducing breast cancer risk • Iodine is low in New Zealand soils- eat seaweed

47. Measuring fat mass, muscle mass and cellular health • Bio-impedance analysis is a tool I use to measure bio-markers of ageing such as fat mass, muscle mass, cellular fluid balance and a marker called phase angle which tests your cellular health. • By losing body fat ,gaining muscle mass and improving the health of your cells you can reduce your risk of chronic disease including cancer.

48. Study done on using phase angle as a predictor of breast cancer outcome • Methods • Of 259 patients the median age at diagnosis was 49 years (range 25 – 74 years). The median phase angle score was 5.6 (range = 1.5 – 8.9). • This study demonstrates that BIA-derived phase angle is an independent prognostic indicator in patients with breast cancer. Nutritional interventions targeted at improving • phase angle could potentially lead to an improved survival in patients with breast cancer.

49. LAUGHTER “A day without laughter is a day wasted” Charlie Chaplin Studies on humour and laughter from Duke University, Loma Linda University, UCLA and others have shown: Laughing helps relax tense muscles. It reduces the production of stress hormones. Laughter and a positive attitude strengthen the immune system. There are no known negative side effects to laughter.

50. UNTOUCHABLE GIRLS • I recommend the Topp Twins film- an inspiring hilarious kiwi journey including a touching tribute to the power of love in overcoming breast cancer.