3. Breast cancer risk factors - overview

(A)  FACTORS PREDISPOSING FOR BREAST CANCER
 

A1 - Compromised detox system

toxic overload

● toxins from food, air, water, dental implants, medications, internal microorganisms. Overburdened and/or compromised by genetic/nutritional deficiencies detox system can't efficiently metabolize and dispose of toxins; toxic metabolites inflict injury by causing oxidative damage or cross-linking with body molecules, including DNA

nutritional deficiencies

● detox function is dependant on the wide spectrum of nutrients

chronic stress
psychological trauma

● negatively affects entire metabolism, detox and other functions

negative emotions

chronic dehydration 

● sufficient water intake is a must for efficient detox function

A2 - Compromised oxidative protection

oxidative exposure

● tobacco smoke, chlorine, pesticides, food additives, drugs, air pollutants, heavy metals, ultraviolet light...

nutritional deficiencies

● oxidative protection depends on many antioxidant nutrients

A3 - Inherent genetic aberrations

BRCA1/2 gene mutation

 ● tumor-suppressor genes, short for BReast CAncer; mutation increases the risk up to tenfold; estimated 5-10% of all breast cancer cases carry mutated BRCA1 or 2

ATM gene mutation

 ● also part of tumor-suppressing mechanism, Ataxia-telangiectasia mutated gene is estimated to be  altered (heterozygous carriers) in up to 1% of women; up to 10% of all breast cancer cases are carriers, possibly more

CHEK2 gene mutation

 ● cell cycle checkpoint regulator gene, acting on signals of DNA damage to prevent cellular division; functionally associated with BRCA1 and TP53; its 1100delC heterozygous polymorphism has estimated <1% incidence and threefold increase in breast cancer risk

TP53 gene mutation

● tumor (suppressor) protein p53 gene is mutated in more than half of all cancers, but only in about 20% of breast cancer cases; however, research indicates that TP53 mutations are nearly three times more frequent in BRCA1/2 germline mutation carriers; TP53 is regulated by CHEK2 (which is, in turn, activated by ATM), which activates TP53 to arrest cell cycle for an attempt at DNA repair, and then breaks it down to prevent apoptosis (programmed cell death) if repair succeeds; illustrates genetic interactions and interdependency 

FOK1 gene mutation

● vitamin D receptor gene, whose proper function is needed for efficient cellular use of vitamin D, which inhibits cell proliferation, and downregulates both estrogen and progesterone receptors; significantly lower risk increase than for above polymorphisms (indicated ~25% for Ff and ~60% for ff FOK1 polymorphism), but much higher incidence (about 40-50% and 10%, respectively)

PALB2 gene mutation

● partner and localizer of BRCA2 protein enables accumulation of BRCA2 protein in the cell nucleus; it is altered in less than 1% of women, doubling the risk of breast cancer

 PTEN gene mutation

 ● another gene encoding tumor-suppressing protein (phosphatase and tension homolog enzyme), PTEN mutations are very rare, usually associated with Cowden syndrome; carriers have up to 6 times higher breast cancer lifetime risk

A4 - Compromised immune system

chronic stress

● stimulates production of adrenal hormones, inhibiting immune function, shrinking the thymus gland and weakening antiviral response

chronic internal infections,
intestinal bacterial/fungal overgrowth,
insufficient rest (sleep) time,
high sugar intake,
high blood lipids,
nutritional deficiencies, smoking, alcohol, overweight,
negative emotions

● poor lifestyle choices negatively affect the immune function

A4 - Other predisposing factors

nutritional deficiencies/imbalances

● compromising detox, antioxidative, and/or cellular function

regular alcohol consumption

● regular, even quite moderate consumption inked with higher blood estrogen levels; other possible mechanisms include increased solubility of carcinogens, interfering with folate metabolism, elevated oxidative stress and mutagenic effects of its primary metabolite, acetaldehyde

tobacco smoke

● contains over 4000 chemicals, most of them toxic, and over 50 known carcinogens

B1 - Radiation exposure

early-life
medical exposures

● radiation exposures before age 20, beginning with fetal exposures and subsequent X-ray and nuclear medicine diagnostic (γ-rays) exposures

mammography

● cumulative doses in extended periods of time can be significant

galactography

● imaging of breast's milk ducts by mammography unit; similar exposure as low-level mammography

other adult chest or whole body exposures

● other radiology diagnostic procedures, occupational exposures, nuclear fallout, smoking (from Polonium 210), air travel, radon, background radiation

non-ionizing radiation
(power field)

● although the evidence is inconclusive, there are clear indications that exposure to non-ionizing radiation can be significant breast cancer risk factor

sexual intercourse,
physical contact, food (grains), 
pets (?)

● human papilloma virus (HPV), mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV) and bovine leukemia virus (BLV) have been identified at higher to much higher incidence in breast cancer patients; each has the ability to alter cellular DNA, transforming normal cells into malignant

industrial chemicals (including food additives, pesticides and herbicides) in construction and household products, food, water and environment

● many chemicals have been identified as carcinogenic, mainly in experiments with laboratory animals; little research is done on the role of unknown number of such chemical carcinogens in the initiation and growth of breast cancer, but it is reasonable to assume it to be significant

C1 - Mitogenic/antiapoptopic hormones

ovarian hormones level/balance

● nominal blood estrogen level is an indicator, although somewhat loose, of the free (bioavailable, active) estrogen, which stimulates cell proliferation; higher estrogen level is likely to result in early menarche and late menopause (also, as a part of the elevated overall hormonal activity, in accelerated growth)
● hormonal balance is regulated by a complex co-action of the pituitary gland and hypothalamus, but also affected by other factors, such as exposures to xenoestrogens (environmental estrogens) or chronic stress

exposure to environmental estrogens (xenoestrogens)

● Phthalates (plasticizers) - chemicals leaking into foods form plastic containers and wraps, tend to accumulate in the body and may disrupt endocrine function
● Pesticides - present in many foods and drinking water, may negatively affect body's regulatory functions, including hormonal
● Detergents, trichloro-ethylene,
PCBs... many environmental chemicals can act as estrogen mimics; level of exposure and individual vulnerability vary, but can be significant
● Cadmium - toxic contaminant present in food, water and environment (also, in tobacco) that steadily accumulates in the body, acting like estrogen; it can also raise testosterone levels, as additional breast cancer risk factor
● Natural food components - some natural food components, for instance, soybean isoflavones genistein and daidzein, can have estrogenic effect; however, Asian populations with high soybean intake have low breast cancer incidence, which suggests that (1) the effect may be more complex, and/or dependant on the overall diet and lifestyle (2) soy isofavones generally act as anti-estrogens, taking estrogen receptors while having much lower estrogenic potency (less than 2%)
● Herbal extracts - natural herbal components can also have estrogenic potency; among commonly used herbs with such compounds are angelica, reishi mushroom, licorice, fo-ti and astragalus (they are all considered healthful, hence the above applies here as well)

elevated insulin

From high-glycemic diet,
insulin resistance, diabetes; insulin stimulates cell division and increases the level of free (active) estrogen

elevated IGF

insulin-like growth factor, mitogenic, antiapoptotic hormone, enhancing estrogen activity, and vice versa; high levels linked to increased risk of several common cancers, including breast cancer

hormonal medical treatments

● lHRT - large trials consistently come up with significantly increased risk
● Birth control pills - the earlier in life starts the use, and the longer it lasts, the more of the risk factor they become
● SERM drugs - Selective Estrogen Receptor Modulator, including those like Tamoxifen, that are used for breast cancer treatment and prevention, evidently are the additional risk factor for some woman

C2 - Compromised immune function

chronic internal infections

● toot/jaw/root canal infections - appears to have significantly higher incidence in breast cancer patients

● often accompanied with leaky gut and nutritional deficiencies, burdens and weakens the immune system

chronic stress

● stimulates production of adrenal hormones, inhibiting immune function, shrinking the thymus gland and weakening protective responses against cancer

insufficient rest (sleep) time, high sugar intake,
high blood lipids, nutritional deficiencies, smoking, alcohol, overweight, negative emotions

● many poor lifestyle choices alone negatively affect immune function, and their combined negative effect is disproportionally larger

C3 - Compromised detox system

● due to toxic overload, toxic intestines (bacterial/fungal overgrowth), leaky gut, nutritional deficiencies, chronic stress and/or
negative emotions, chronic dehydration 

C4 - Genetic aberrations

● compromising cell cycle control and immune system efficiency

C5 - Other promoting factors

nutritional deficiencies/imbalances

● high-glycemic diet - causing elevated blood level of both, insulin (with or without insulin insensitivity) and IGF, which promotes cell proliferation similarly to estrogen
● high-sugar diet - in addition to being a high-glycemic food, sugar inhibits the immune system; higher rate of glycolysis (burning glucose for energy within cell) increases concentration of its by-product, lactic acid, making cell more acidic, hence compromising its optimum functioning
● low fiber - evidence supports inverse relationship between dietary fiber intake and breast cancer risk
● specific mineral/vitamin deficiencies compromising detox, immune, and/or cellular function

regular alcohol consumption

● regular, even quite moderate consumption inked with higher blood estrogen levels; other possible mechanisms include increased solubility of carcinogens, interfering with folate metabolism, elevated oxidative stress and mutagenic effects of its primary metabolite, acetaldehyde

smoking

● contains over 4000 chemicals, most of them toxic, and over 50 known carcinogens

low melatonin

● melatonin is an estrogen antagonist hormone; it also acts as antioxidant, antimitotic and immune-enhancing agent; body produces melatonin mainly during nighttime sleep, in darkness; thus lack of nighttime sleep, or lighted room, inhibit melatonin production, and so does exposure to power (electrical) field

● the risk seems to become the more significant the longer bra is worn over several hours a day, on daily basis

overweight/obesity

● according to research data, overweight and obesity are risk factors for postmenopausal women;

weight gain (postmenopausal)

● can enhance estrogen production and lead to estrogen dominance state

lean body (premenopausal)

● if resulting from diet restriction,
metabolic disturbance or deficiency

insufficient/inadequate checkups

● latter stages at the time of diagnosis significantly lower chances for recovery
● risk of false negatives,
compression risk, radiation risk