Epigenetic Factors to Reduce Breast Cancer Risk – Part 1

Epigenetic factors to reduce breast cancer risk has been a particular interest of mine ever since I found out that I had breast cancer in 2004. I have studied everything I could lay my hands on with reference to epigenetic factors. The word means “above genetics” and is the science of how genes can be expressed differently using external factors without changing the DNA structure of those genes.

The reason epigenetics interests me so greatly is because I lost both my mother and my grandmother to breast cancer. When I was subsequently diagnosed with breast cancer myself, I was quite concerned about the so-called genetic aspect of this disease. I spoke about this with a friend of mine and I can remember saying to her “What if everything I’m doing to get well and stay well turns out not to be enough if I’m genetically predisposed to breast cancer?” Her response was to introduce me to a scientist named Bruce Lipton and a whole new way of thinking. Dr Lipton’s book “The Biology of Belief” helped me to understand that we do not have to be slaves to our genes. The book introduced me to the  concept of epigenetic factors which can influence the expression of genes.

I learned that nutrition, thoughts, exercise and quite a few other factors can influence our genes in a very powerful way. What an immensely liberating thought – that we mere humans can play a huge role in turning off the very genes that might otherwise predispose us to breast cancer.

In a series of articles, I will be sharing some of the epigenetic nutrients that provide us with the ability to alter genetic expression, thus possibly preventing or reversing breast cancer. From my best count, here are the best 11 ways they do this (and one article will be devoted to each subject):

Epigenetic nutrients can:

1. Control regulatory genes
2. Prevent damage to DNA
3. Prevent rapid cell proliferation
4. Ease or prevent cancer-promoting inflammation
5. Change malignant cells into healthy cells
6. Restore receptors on cells
7. Inhibit excess estrogen production
8. Trigger cancer cell death (apoptosis)
9. Block growth factors
10. Block angiogenesis
11. Prevent metastasis

PART 1 – NUTRIENTS THAT CAN CONTROL REGULATORY GENES

Through genetic testing, we know that there are a number of gene defects that can predispose a person to certain diseases, including breast cancer. There are quite literally hundreds of ways genes can be influenced to control, slow or stop breast cancer growth. Any of these genes, when faulty, damaged or disrupted, can put us at a higher risk for breast cancer. Fortunately, there are a number of nutrients that have epigenetic targets in cancer cells and they block these processes, and can help to prevent carcinogenesis (formation of cancer cells).

Here are but a few of the most-studied genes involved with breast cancer:

MTHFR

The MTHFR gene plays a critical role in DNA methylation. This is a much-studied and ever-expanding subject, especially for breast cancer patients. According to 2012 research done at the University of Mississippi, a number of genes become abnormally methylated in breast cancer patients. [1] Methylation involves the addition or removal of a methyl group (CH₃) to a substance so that it can metabolized. Methylation takes place daily inside cells, millions of times,  and requires the presence of enzymes known as DNA methyltransferases (DNMTs) to catalyze (cause or accelerate) the process.

For example, methylation is required to convert the neurotransmitter serotonin into melatonin. Methylation is involved in converting stronger estrogens into less aggressive estrogens and that is one of the reasons it is included in this discussion. MTHFR working properly means you can break down circulating estrogen and excrete it, otherwise it can build up to dangerously high levels and this increases breast cancer risk. Hypermethylation is known to be associated with estrogen receptor-positive breast cancer. [2]

The problem isn’t just with estrogen, however. MTHFR also provides the directions to produce an enzyme called methylene tetrahydrofolate reductase, which converts inactive folate (vitamin B9) to its active form, levomefolic acid, to enable cells to utilize it. An inability to convert folate into levomefolic acid affects many metabolic processes in the body. Active folate is essential for healthy cell division, DNA synthesis and repair, heart health, good vision, brain development, memory and mood, and so much more.

Helpful Nutrients:

Epigallocatechin-3-gallate – EGCG – found in found in amla, black tea, carob flour, cranberries (raw), green tea, hazelnuts, oolong tea, peas, pecans, pomegranates [3]
Curcumin  – from turmeric [4]
Genistein – found in chickpeas, dates, kidney beans, lupin, peanuts, peas, pomegranates, quinoa, soybeans & soy products [5]
Lycopene – found in apricots, asparagus, beets, bell peppers (red), bitter melon, carrots, cucumbers, dragon fruit, goji, grapefruit, guava, mangoes, noni, papaya, passionfruit, persimmons, pistachio nuts, tomatoes, red beans, watermelon [5]
Resveratrol – found in acai, black beans, black raspberries, blueberries, cassava, cranberries, dark chocolate, grapes (red, not green grapes), lentils, lingonberries, mulberries, peanuts, peanut butter, pistachio nuts, raspberries, strawberries [6]
Caffeic acid – found in adzuki beans, amaranth, apples, apricots, arugula (rocket), asparagus, barley, bee propolis, beets, bitter melon, blackberries, black raspberries, blackcurrants, blueberries, broccoli, Brussel sprouts, buckwheat, buckwheat bran, brown rice, cabbage, cantaloupe, carrots, cauliflower, celery, chia seeds, chickpeas, chilies and hot peppers, coffee, collard greens, corn, cranberries, daikon, dandelion greens, dates, durian, eggplant, einkorn, flaxseed, goji/wolfberry, grapefruit, grapes, graviola, hazelnuts, honeydew melon, kale, kiwi, lemons, lentils, lima beans, lingonberries, lychee, mandarins, mangosteen, maqui, mulberries, nectarines, oats, papaya, peaches, pears, peanuts, peas, pine nuts, pineapple, plums, pomegranates, pumpkin seeds, quinoa, radishes, raspberries, sorghum bran, soybeans, spinach, strawberries, sunflower seeds, tomatoes, turnips, wasabi [7]
Chlorogenic acid – found in almonds, apples, artichoke, avocados, bell peppers, bitter melon, black beans, black raspberries, blackberries, blackcurrants, blueberries, carrots, cassava, cherries, chia seeds, chickpeas, chilies and hot peppers, coffee beans, cranberries, dandelion greens, durian, eggplant, figs, goji, grapefruit, graviola, guava, kiwi, kohlrabi, lemons, lentils, lingonberries, lychee, mulberries, nectarines, passionfruit, peaches, peanuts, pears, plums, pomegranates, raspberries, rice bran, spinach, sunflower seeds, tomatoes [7]

BRCA1, BRCA2

Much-studied genes, BRCA1 and BRCA2 stand for breast cancer type 1 and type 2 susceptibility proteins. They provide instructions for the creation of proteins that repair damaged DNA and act as tumor suppressors. Having a mutated BRCA1/2 gene has been shown to put a person at a higher risk for breast cancer, ovarian and some other cancers. It is estimated that around 10% of breast cancer cases are caused by mutations in these genes. DNA methylation can be involved here too – a 2014 Chinese study investigating the regulation of DNMT1 (discussed above) in BRCA1-mutated breast cancer found that a transcription factor known as E2F1 was hypermethylated. Another key factor is a process known as histone deacetylation. Without getting into huge detail requiring a chemistry degree to understand it, acetylation of histones involves DNA binding proteins, activation of gene transcription and other cellular functions.  [8] Fortunately, there are a good many nutrients that can play a protective role for those with BRCA1/2 mutations:

Helpful Nutrients:

Genistein – found in chickpeas, dates, kidney beans, lupin, peanuts, peas, pomegranates, quinoa, soybeans & soy products [9]
Epigallocatechin-3-gallate – EGCG, found in amla, black tea, carob flour, cranberries (raw), green tea, hazelnuts, oolong tea, peas, pecans, pomegranates [9]
Soy foods [10]
Sulforaphane – from broccoli sprouts, cruciferous vegetables [11]
Garlic [11]
Caffeic acid – found in adzuki beans, amaranth, apples, apricots, arugula (rocket), asparagus, barley, bee propolis, beets, bitter melon, blackberries, black raspberries, blackcurrants, blueberries, broccoli, Brussel sprouts, buckwheat, buckwheat bran, brown rice, cabbage, cantaloupe, carrots, cauliflower, celery, chia seeds, chickpeas, chilies and hot peppers, coffee, collard greens, corn, cranberries, daikon, dandelion greens, dates, durian, eggplant, einkorn, flaxseed, goji/wolfberry, grapefruit, grapes, graviola, hazelnuts, honeydew melon, kale, kiwi, lemons, lentils, lima beans, lingonberries, lychee, mandarins, mangosteen, maqui, mulberries, nectarines, oats, papaya, peaches, pears, peanuts, peas, pine nuts, pineapple, plums, pomegranates, pumpkin seeds, quinoa, radishes, raspberries, sorghum bran, soybeans, spinach, strawberries, sunflower seeds, tomatoes, turnips, wasabi [7]
Chlorogenic acid – found in almonds, apples, artichoke, avocados, bell peppers, bitter melon, black beans, black raspberries, blackberries, blackcurrants, blueberries, carrots, cassava, cherries, chia seeds, chickpeas, chilies and hot peppers, coffee beans, cranberries, dandelion greens, durian, eggplant, figs, goji, grapefruit, graviola, guava, kiwi, kohlrabi, lemons, lentils, lingonberries, lychee, mulberries, nectarines, passionfruit, peaches, peanuts, pears, plums, pomegranates, raspberries, rice bran, spinach, sunflower seeds, tomatoes [7]
Resveratrol – found in acai, black beans, black raspberries, blueberries, cassava, cranberries, dark chocolate, grapes (red, not green grapes), lentils, lingonberries, mulberries, peanuts, peanut butter, pistachio nuts, raspberries, strawberries [12]
Vitamin D3 [13]

Special note for BRCA1/2 mutation carriers – when taking B-vitamins, carriers of the BRCA1/2 mutation would be well advised to consult a functional medicine doctor or integrative oncologist specifically trained to deal with this genetic mutation, because there are conflicting studies on the helpfulness of B vitamins for carriers of this mutation. One study reported that high folate levels were associated with an increased risk of breast cancer for BRCA1/2 mutation carriers [14] while another study indicated high folate levels were protective. [15]

Remember too that physical activity has also been found to be associated with a reduction in risk of breast cancer for those with BRCA1/2 mutations. [16]

P53

P53 is a tumor suppressor gene, regulating cell division by keeping cells from proliferating (growing and dividing too fast) or in an uncontrolled way. So you want this one to be working because when P53 is faulty, there is seen to be an associated increase in cancer risk. P53 is considered to be one of the most frequently mutated genes leading to cancer development.

Helpful Nutrients:

Quercetin – found in adzuki beans, almonds, amla, Anasazi beans, apples with peels, apricots, artichoke, arugula (rocket), asparagus, avocados, bananas, barley, beets, bell peppers, bilberries, black beans, black-eyed peas, black raspberries, black rice, black tea, blackberries, blackcurrants, blueberries, bok choy, Brazil nuts, broccoli, brown rice, Brussel sprouts, buckwheat, buckwheat bran, cantaloupe, capers, cauliflower, celery, cherries, chickpeas, chia seeds, chilies and hot peppers, cocoa powder (unsweetened), collard greens, corn, cranberries, cucumbers, daikon, dandelion greens, dates, dill, dragon fruit, durian, eggplant, elderberries, figs, gingko biloba, goji, grapefruit, grapes, graviola, green beans, green pepper, green tea, guava, honey, honeydew melon, horseradish, kale, kiwi, kohlrabi, lemons, lentils, lettuce (esp Romaine), lima beans, limes, lingonberries, lychee, mangoes, maqui, mulberries, nectarines, noni, onions, parsley, passionfruit, peaches, pears with peels, peas, peppers, persimmons, pineapple, plums, pomegranates, pumpkin seeds, quinoa, radishes, raspberries, red onions, rutabaga, sage, sesame seeds, shallots, spelt, spinach, strawberries, sunflower seeds, tea (black and green), tomatoes, turnips, watercress, yellow snap beans
[17]
Zinc – found in adzuki beans, almonds, amaranth, amla, apples, apricots, artichoke, arugula, asparagus, avocados, bananas, barley, beets, bilberries, black beans, black-eyed peas, black raspberries, blackberries, bok choy, Brazil nuts, broccoli, Brussel sprouts, cabbage, cantaloupe, carrots, cashews, cauliflower, cherries, chia seeds, chickpeas, collard greens, corn, dandelion greens, dates, durian, eggplant, einkorn, flaxseed, grapefruit, grapes, guava, hemp seeds, honeydew melon, horseradish, jamun, kidney/cannellini beans, kiwi fruit, lentils, lima beans, lingonberries, lupin, macadamia nuts, mangoes, mangosteen, mulberries, nectarines, noni, oats, oranges, papaya, peaches, peanuts, pears, peas, persimmons, pine nuts, pineapple, pistachio nuts, plums, pomegranates, pumpkin seeds, quinoa, radishes, raspberries, red beans, rutabaga, sesame seeds, soybeans, spelt, spinach, strawberries, sunflower seeds, tangerines, tomatoes, turnips, walnuts, wasabi, watermelon, wheat bran [18]
Apigenin – found in artichoke, asparagus, bell peppers, brown rice, cabbage, celery, chamomile tea, chickpeas, chilies and hot peppers, cucumber, dandelion greens, dates, eggplant, elderberries, grapefruit, guava, lemons, limes, lupin, onions, oranges, parsley, passionfruit, peas, pigeon pea leaves, pomegranates, pumpkin seeds, radishes, rice bran, sorghum bran, spelt, strawberries, sunflower seeds, watercress [19]
Vitamin D3 [20]
Arenobufagin – isolated from Chan Su, a Traditional Chinese Medicine herb, aka Venenum Bufonis [21] (please work with a TCM doctor when using this)
Berberine – found in goldenseal, barberry [22]

EZH2

EZH2 is a gene that has been shown in research to be a marker for more aggressive breast cancer. One study indicated “Aberrant expression of EZH2 has been associated with metastasis and poor prognosis in cancer patients.” [23]

Helpful Nutrients:

Omega 3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) [23]
Ginsenoside RH2 – from Korean red ginseng [24]
Epigallocatechin-3-gallate (EGCG) – found in found in amla, black tea, carob flour, cranberries (raw), green tea, hazelnuts, oolong tea, peas, pecans, pomegranates [25]
Curcumin – found in turmeric [26]
Sulforaphane – found in cruciferous vegetables, ie arugula (rocket), bok choy, broccoli, broccoli sprouts, Brussel sprouts, cabbage, cauliflower, collard greens, daikon, horseradish, kale, kohlrabi, radishes, rutabaga, turnips, watercress [27]
Berberine – found in goldenseal, barberry [28]
Tanshindiol – from the Traditional Chinese Medicine herb, Danshen, or Salvia miltiorrhiza [29]
Melatonin – found in bananas, barley, black rice, cherries (esp sour), ginger, grapes, oats, tomatoes, walnuts [30]

This is by no means an exhaustive list of regulatory genes, nor the nutrients that help to influence them. The purpose of this article is merely to inform you of some of the ones that do exist and as I find more, I will add them to this list. As you look through these lists of epigenetic nutrients, you begin to notice the repetition of a few, right? I think it’s pretty clear that those are the ones to focus upon and add to your daily protocols.

IMPORTANT NOTE: Please do not attempt to heal cancer using only a few nutrients. Cancer is a complex process and requires a multi-disciplinary approach. It’s always best to work with an oncologist and/or integrative oncologist and/or oncology naturopath and/or functional medicine doctor to achieve the best results.

References:

[1] Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome – https://www.ncbi.nlm.nih.gov/pubmed/21992498

[2] DNA methylation and hormone receptor status in breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754852/

[3] Suppressive Effects of Tea Catechins on Breast Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997373/

[4] Epigenetic diet: impact on the epigenome and cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197720/

[5] Modulation of gene methylation by genistein or lycopene in breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/18181168

[6] Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392022/

[7] Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols – https://www.ncbi.nlm.nih.gov/pubmed/16081510

[8] Regulation of DNA methyltransferase 1 transcription in BRCA1-mutated breast cancer: a novel crosstalk between E2F1 motif hypermethylation and loss of histone H3 lysine 9 acetylation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936805/

[9] Reversal Effects of Genistein and (-)-Epigallocatechin-3-Gallate on Repression of BRCA-1 Expression in Human Breast Cancer Cells with Activated AhR – http://www.fasebj.org/content/30/1_Supplement/42.6.short

[10] Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study – http://ajcn.nutrition.org/content/early/2013/10/23/ajcn.112.057760.abstract

[11] Modulation of Histone Deacetylase Activity by Dietary Isothiocyanates and Allyl Sulfides: Studies with Sulforaphane and Garlic Organosulfur Compounds – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701665/

[12] Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation – http://www.pnas.org/content/109/20/7765

[13] Cooperation between BRCA1 and vitamin D is critical for histone acetylation of the p21waf1 promoter and for growth inhibition of breast cancer cells and cancer stem-like cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322975/

[14] Plasma folate, vitamin B-6, and vitamin B-12 and breast cancer risk in BRCA1- and BRCA2-mutation carriers: a prospective study – http://ajcn.nutrition.org/content/early/2016/07/26/ajcn.116.133470

[15] The effects of plasma folate and other B vitamins on breast cancer risk in BRCA1 and BRCA2 mutation carriers – http://cancerres.aacrjournals.org/content/75/15_Supplement/LB-185

[16] Effects of lifestyle and diet as modifiers of risk of breast cancer (BC) in BRCA1 and BRCA2 carriers – http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.1505

[17] Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line – https://www.ncbi.nlm.nih.gov/pubmed/26311153

[18] Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells – http://www.nature.com/onc/journal/v19/n46/full/1203907a.html

[19] Evidence for activation of mutated p53 by apigenin in human pancreatic cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277744/

[20] 1,25-Dihydroxyvitamin D3 regulates T lymphocyte proliferation through activation of P53 and inhibition of ERK1/2 signaling pathway in children with Kawasaki disease – https://www.ncbi.nlm.nih.gov/pubmed/28925469

[21] Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway – https://www.ncbi.nlm.nih.gov/pubmed/28892004

[22] Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer – https://www.ncbi.nlm.nih.gov/pubmed/28775788

[23] Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832544/

[24] 20(S)-Ginsenoside Rh2 suppresses proliferation and migration of hepatocellular carcinoma cells by targeting EZH2 to regulate CDKN2A-2B gene cluster transcription – https://www.ncbi.nlm.nih.gov/pubmed/28928088

[25] (-)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/28925507

[26] Effect and mechanism of curcumin on EZH2 – miR-101 regulatory feedback loop in multiple myeloma – https://www.ncbi.nlm.nih.gov/pubmed/28322158

[27] The Ezh2 Polycomb Group Protein Drives an Aggressive Phenotype in Melanoma Cancer Stem Cells and is a Target of Diet Derived Sulforaphane – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919248/

[28] Naturally occurring anti-cancer agents targeting EZH2 – https://www.ncbi.nlm.nih.gov/pubmed/28323035

[29] Biological evaluation of tanshindiols as EZH2 histone methyltransferase inhibitors – https://www.ncbi.nlm.nih.gov/pubmed/24767850

[30] Melatonin inhibits tumorigenicity of glioblastoma stem-like cells via the AKT-EZH2-STAT3 signaling axis – https://www.ncbi.nlm.nih.gov/pubmed/27121240

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