BRCA gene, epigenetics and cancer news
(NaturalHealth365) The fundamental debate that both gives rise to and exercises the human psyche existed long before Socrates exposed the fundamentally flawed concept of human intelligence in ancient Greece. And this perpetual conundrum continues with the same ferocity to the present today – especially when it comes to understanding the concept of epigenetics and cancer risk.
All that has changed throughout the eons are names and faces, but not the basic ‘argument’…
Epigentics and cancer: A major debate between modern and traditional medicine
So, which is it? Chicken or egg … which one produces the other?
Mind or behavior … does the mind determine behavior or is it a consequence of behavior?
Figure or ground perception – words on paper, horse in a field – which is the most important?
Germ or milieu … Does the germ produce infection or does the environment permit the germ to live and propagate (infection)?
Epigenetics or genetics … which one determines genetic expression – the original program of the DNA (genes) or the environment in which the genes exists?
Cancer lessons learned from Angelina Jolie
As most people know, Angelina Jolie had both of her breasts surgically removed even though there was absolutely no sign of breast cancer in either breast. And furthermore, she has already planned to have both of her healthy ovaries removed, as soon as she has recovered sufficiently from the first surgery.
Clearly, those promoting the genetic side of the argument have been more convincing than those promoting the epigenetic perspective.
Briefly, BRCA genes refer to genes that exist in all people and whose function is to repair damaged, double stranded DNA. If one of the parents have a mutation in this gene, 50% of the children are likely to have the same mutation hence this mutation exists equally in both sexes.
In order for this mutated inheritance to be a problem, the second gene, which was passed from the parent without the BRCA mutation, must undergo what is called, somatic mutation (a mutation occurring after birth).
In other words, the normal gene that was inherited must be damaged after birth to the degree that a mutation is produced resulting in both genes being defective. Even when this happens it is only the first step in the process since the BRCA genes are only one set of an entire group of enzymes that are involved in DNA repair.
What really affects our genes and cancer risk?
For these reasons, BRCA genes are said to be capable of “skipping” generations. In reality, genes do not “skip” generations. The offspring who inherits the mutated gene simply does not have enough toxic exposure to damage the other, non-mutated BRCA gene.
Toxic exposure is epigenetics….that is, the environment in which the cell lives. If the interstitial fluid (matrix) surrounding the cells is sufficiently toxic, the BRCA genes, as well as all other genes are at risk of being damaged, and if not repaired adequately, mutated.
The vast majority of cellular damage takes place at the outer cellular membranes (double layered) and, if significant to the point that a break occurs, the cytoplasm, or inside of the cell becomes exposed and possibly damaged. Clearly then, it is a long way to the nucleus where the DNA is housed within another double layered membrane, the nuclear membrane.
Somatic mutations (occurring after birth) accordingly, require a continual, highly toxic set of conditions in order for them to occur. Unfortunately, those circumstances are currently the norm on planet Earth but nonetheless, it should be easily recognized that a set of environmental (epigenetic) stimuli is required to allow an inherited mutation (e.g., BRCA) to progress into a cancerous transformation.
How human cells are affected by our environment
Cells are designed to function in sequence with and respond to conditions in their immediate living environment, which is known as the extracellular fluid or matrix. They have no function independent of their environment. They may be said to be contiguous with their environment or that both the cells and their environment are constituents of a larger whole such as an organ. There is no cellular function in isolation.
Cellular membranes (“skin”) are the mediators between the extracellular (fluid/matrix) environment and the internal cellular environment and functioning. Membranes contain thousands of “pores”, “gates”, ”channels”, receptors and antennae, which determine cellular function based upon environmental conditions.
The DNA, housed in the nucleus (center) of the cell functions as a reproductive “organ” of the cell generating products in accordance with the “instructions” it receives from the cellular membranes. Hence, genetic expression is always and only in response to the cellular needs as determined by the membranes as a consequence of the environmental (epigenetic) conditions.
“Up-regulation” and “down-regulation” describe normal cellular functioning. Down-regulation is the process by which cells decrease the amount of a cellular component in response to an external condition, while an increase of a cellular component is called up-regulation.
For example, if a particular receptor is lacking or deficient such that normal cellular functions cannot occur; more receptors are produced by the DNA and transported to the outer membrane so that the cell can be brought back into homeostasis (balance). When this occurs, the cell is said to have “up-regulated” the receptor, as is what occurs to the cells lining the uterus during the first third of the menstrual cycle.
Uterine cells become more “sensitive” to estrogen simply by increasing the number of estrogen receptors (up-regulating estrogen receptors). Likewise, if a cell is being over stimulated throughout a relatively prolonged period, the production of these receptors by the DNA is decreased in order to protect the cell and maintain homeostasis.
This physiological homeostatic process is known as tachyphylaxis and is what occurs when cells are exposed to excessive amount of sugar. They down-regulate insulin receptors and the person is said to be “insulin resistant”.
This is the fundamental mechanism by which the body is able to very accurately and precisely modulate hormone production as is required for growth, development, reproduction, optimal functioning and homeostasis. Individual cells contribute in mass with all the other cells of an organ or organ system to maintain the harmonic resonance of the 100 trillion + cells in the body.
This continual modulation or hormones and receptors, as well as all other cellular products is called by physiologists as “positive” and “negative feedback loops”. These feedback loops maintain appropriate and optimal levels of hormones as the environment changes, whether from stimuli external to the body (trauma, EMF, pesticide ingestion, etc) or changes occurring within the body, such as growth or intestinal floral changes, for example.
Science reveals how the environment affects genetic expression and cancer risk
The Institute of Pathology (University Hospital Nijmegen) in the Netherlands published a study in 1995 wherein they were able to show that the angiogenic (new blood vessel formation) factors responsible for tumor growth and metastases (spread) could be manipulated by altering the oxygen concentration in the environment of the cells.
In other words, when the oxygen concentration was lowered, the gene expression of VPF (vascular permeability factor) increased. VPF is also known as vascular endothelial growth factor (VEGF), hence when the oxygen concentration around cells decreases, the cells’ response is to produce more blood vessels in order to bring more blood carrying oxygen to the cells.
It is well known that cancer is an anaerobic, homeostatic response to a low oxygen environment. Hence, as the oxygen concentration continues to be low, cancer will develop, grow and spread by inducing the increased production of these proteins, which produce new blood vessels. “…epigenetic events….represent fundamental aspects of cancer, and play key roles in neoplastic transformation and tumor progression”, Matouk, et. Al, Institute of Medical Science, University of Toronto.
Simply put, epigenetics regulate whether or not a gene will be turned on or off that, in turn allows tumors to develop, grow and spread. And, that phenomenon does not involve mutations. It is basically the same set of homeostatic responses that allows for all other physiological functions to occur, such as hormone levels, as discussed.
These same authors went on the state, “Recent evidence suggests that epigenetic mechanisms play a major role in breast carcinogenesis, contributing to genetic instability in breast cancer….including cell cycle control genes (p161NK4a), steroid receptor genes (Era, PR, RARB2), tumor suppressor genes (BRCA1)and others.”
Their conclusions are that breast and other cancers develop, grow and spread as a result of epigenetics, or microenvironment around cells. It is epigenetics that control genetic expression and it is abundantly clear from their last statement that, estrogen, progesterone and BRCA mutations all contribute to breast cancer development and progression only if the environment of the cells stimulate this malignant genetic expression.
Anderson, et. Al., from the University of Michigan published their review of the literature regarding nutrient status and the generation of DNA methylation, which has been shown to be the mechanism whereby epigenetics regulate genetic expression. One-carbon metabolism (methylation) is the result of several enzymes in the presence of dietary micronutrients, which include but are not limited to folate, choline, betaine and other B vitamins. For this reason, nutrition status, particularly micronutrient intake, has been a focal point when investigating epigenetic mechanisms.
Furthermore, the ingested substances referred to as macronutrients (carbs, proteins and fats) actually supply the basic raw materials necessary for repair, renewal and new cell development. In summary, macronutrients supply the materials for regeneration, rejuvenation and procreation while micronutrients provide the mechanisms by which this all occurs.
The quality and quantity of our food intake directly contributes to whether or not we will develop cancer by turning off tumor suppressor genes and/or turning on other genes permitting tumor growth and metastases. In fact, these same authors were able to glean from their review and integration of human epidemiological data with that of animal studies that it is not only the mothers’ nutritional status that contribute to the child’s health, but also that of the grandmother’s, as well.
“As parents, we have to understand better that our responsibilities to our children are not only of a social, economical, or educational nature, but that our own biological status can contribute to the fate of our children, and this effect can be long-lasting,” said Mihai Niculescu, M.D., Ph.D., study author from Nutrition Research Institute at the University of North Carolina at Chapel Hill, in Chapel Hill, N.C.
At the most rudimentary biochemical level underlying all of these metabolic processes are redox reactions, which are responsible for metabolism (gene expression, protein production, repair, new cell production, etc.). That is, oxidation and anti-oxidation (reduction) are how life happens.
Keep in mind that the redox potential, like pH (acid-alkaline), is a fundamental quality of the cellular environment, or epigenetics and is largely a function of (dependent upon) nutritional intake and waste removal mechanisms.
Social genomics or the effect of psychological and social influences on genetic expression has become a very broad field of study with a vast amount of solid, scientific research having been accumulated over the past few decades.
This field actually emerged in the modern era several decades ago when Hans Selye, MD, PhD (pioneering endocrinologist) identified and coined the expression, “stress” pertaining to the psychology of the individual, rather than physical influences. The mind (or brain’s) perception of the social environment and its likelihood to impact the individual are translated into physiology, biochemistry and genetics through the regulation of hormones, neurotransmitters, and other signaling molecules that activate membrane receptors and transcription factors, etc.
A very simple example is the “fright or flight” response wherein the sympathetic nervous system and the connection between the brain and the adrenal glands (hypothalamic-pituitary-adrenal axis) represent two pathways by which perceptions of negative social conditions regulate gene transcription in multiple ways in a multitude of cells. Positive psychological conditions, such as meditation, prayer and joy also regulate human gene expression although the molecular mediators are poorly understood at present.
Although DNA encodes the potential for a cell’s activities, that potential can only become realized if the gene is expressed. Without being expressed, genes are no more relevant than a map lying on the floor in the backseat of the car.
So, with all of that in mind, it might be concluded that epigenetics is the answer to “which is it”, genetics or epigenetics? The answer lies in the ability to engage in self dialectics.
Simply ask yourself, which is more important, my back or my front? Stars or space? In or out? As a moments’ reflection will reveal to you, they are both aspects of the same phenomenon and cannot be separated. And, in fact it is the question, “which is it?” that is the problem.
The answer, of course is neither….it is both because they are two fundamental aspects of the same thing. Separating them is artificial since they are not separated anywhere except in our minds.
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About the author: For the first ten years of his medical career, Thomas Lodi, MD, MD(H), CNS worked in conventional settings as an internal medicine specialist, urgent care physician, and as an intensivist in ICU and CCU departments of various hospitals. Although he occasionally sees patients with a variety of medical conditions, Dr. Lodi, has narrowed his scope of practice through specific training and extensive experience over the past 12 years to Integrative Oncology (caring for people with cancer) through his treatment center, An Oasis of Healing. For more information about Dr. Lodi – visit: An Oasis of Healing
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