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Stress and the Spread of Cancer

Though it's clearly not a simple matter of cause and effect, the theory that stress is somehow related to cancer is a persistent one. There have been several long-range research studies that investigated a possible connection, but results were contradictory. However, a lab study from cancer biologists at Wake Forest University School of Medicine in Winston-Salem, North Carolina, recently found new evidence on the impact of the stress hormone epinephrine on cancers of the breast and prostate. Now we may be on the way to understanding this complex relationship better, and learning whether stress may actually cause cancer... or just causes the body to lose its ability to fight it.


The adrenal glands, which sit on the kidneys, produce epinephrine, also known as adrenaline. The body uses this hormone like a power tool at times of stress, but when stress is prolonged, the adrenals continue to pump out the hormone and levels remain elevated. Wondering how the excess epinephrine affects cancer cells, and by what process, researchers exposed breast and prostate cancer cells to the hormone in the lab. What's supposed to happen in the body, normally, is that a protein with the peculiar name of "BAD" helps trigger naturally occurring cell death, called apoptosis -- but when epinephrine comes into contact with BAD, as the researchers discovered, it activates enzymes that inactivate BAD and the cells continue to grow.

This might be one way high stress connects to cancer... unchecked by BAD, the cancerous cells continue on their destructive path. This discovery could help explain a previous Canadian study's finding that men who had taken beta blocker drugs for hypertension for at least four years had an 18% lower risk of developing prostate cancer... since beta blockers block the effects of epinephrine. Also, even more recently, another study published in the Journal of Psychosomatic Research, demonstrated that in patients with metastatic breast cancer, stressful or traumatic life events reduced the "median disease-free interval" to 30 months from 62.


George Kulik, PhD, was one of the study's lead authors. When I called him he told me that not all types of cancer cells respond this way to stress hormones, so one priority is identifying which ones do. One reason past studies on stress and cancer have not been able to show a relationship could be because not all cancers are shown to react to epinephrine and Dr. Kulik suspects only 5% to 10% may be affected by the hormone. Dr. Kulik explained that in a large population study, these would be "washed out" in the overall findings. But once researchers know which cancer cells respond, they will have the opportunity to study them more closely.


In some ways it almost seems like a bad joke -- a cancer diagnosis is highly stressful for anyone to have and obviously a time that stress hormones are likely to soar. It's not known whether epinephrine has an impact on the development of cancerous cells but, according to Dr. Kulik, the presence of stress hormones might interfere with cancer care because treatment is designed to trigger apoptosis of the diseased cells. Dr. Kulik and his colleagues are now working to learn more about the impact of stress hormones on individual patients, which he says will be aided by the fact that it is already possible to identify the level of stress hormones people have.

His team has now moved from experiments in the lab to doing them with mice. However, there is no reason to wait to develop better awareness of personal stress levels and to build an arsenal of tools to handle stress more successfully. Immediate responses to the acute stress of, say, receiving disappointing news or being anxious about a big event should include deep breathing, quiet music and other practices that are instantly soothing. For longer-term stress, such as day-to-day parenting challenges, a difficult job situation, or, for that matter, a cancer diagnosis, it is useful to develop stress management skills, which may include meditation, self-hypnosis, exercise and other techniques that calm the mind and the body. You can learn these in formal classes frequently found at community centers, YMCAs and the like, but there are also many books and CDs that are extremely helpful in practicing these techniques at home. Since stress has certainly been linked to other diseases as well, you can't lose by focusing on managing your stress.

Source(s): George Kulik, PhD, assistant professor of cancer biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.


Stress And Heart Disease
Type A Behavior and Heart Disease
 Prevention and Treatment of Heart Disease, Heart Disease and Job Stress

The relationship between stress, heart disease and sudden death has been recognized since antiquity. The incidence of heart attacks and sudden death have been shown to increase significantly following the acute stress of natural disasters like hurricanes, earthquakes and tsunamis and as a consequence of any severe stressor that evokes "fight or flight' responses. Coronary heart disease is also much more common in individuals subjected to chronic stress and recent research has focused on how to identify and prevent this growing problem, particularly with respect to job stress. In many instances, we create our own stress that contributes to coronary disease by smoking and other faulty lifestyles or because of dangerous traits like excess anger, hostility, aggressiveness, time urgency, inappropriate competitiveness and preoccupation with work. These are characteristic of Type A coronary prone behavior, now recognized to be as significant a risk factor for heart attacks and coronary events as cigarette consumption, elevated cholesterol and blood pressure. While Type A behavior can also increase the likelihood of these standard risk factors, its strong correlation with coronary heart disease persists even when these influences have been excluded. However, there is considerable confusion about how to diagnose and measure Type A behavior and numerous misconceptions about which components are the most as indicated in the Interview with Dr. Ray Rosenman, one of the co-authors of the Type A behavior concept. The following discussion is designed to clarify these and other aspects of the role of emotions and behavior in heart disease and how this may relate to the explosive increase in job stress. References have also been provided to obtain additional details on items that may be of special interest.

Stress is the condition that results when person-environment transactions lead the individual to perceive a discrepancy, whether real or not, between the demands of a situation and the resources of the person's biological, psychological or social systems. In medical terms, stress is the disruption of homeostasis through physical or psychological stimuli. Stressful stimuli can be mental, physiological, anatomical or physical reactions. The term 'stress' in this context was coined by Austro-Canadian endocrinologist Hans Selye, who defined the General Adaptation Syndrome or GAS paradigm in 1936.

Types of stress
Richard Lazarus published in 1974 a model dividing stress into eustress and distress. Where stress enhances function (physical or mental, such as through strength training or challenging work) it may be considered eustress. Persistent stress that is not resolved through coping or adaptation (distress) may lead to escape (anxiety) or withdrawal (depression) behavior.

The difference between experiences which result in eustress or distress is determined by the disparity between an experience (real or imagined), personal expectations and resources to cope with the stress. A person living in a fashion consistent with personally-accepted expectations may have no stress even if the conditions might be interpreted as adverse from some outside perspective — rural people may live in comparative poverty, and yet be unstressed if their resources are sufficient to meet their needs and expectations. If there is chronic disparity between experience and expectations, stress may be relieved by adjustment of expectations to meet the ongoing experiences or conditions. Alarming experiences, either real or imagined, can trigger a stress response.

Adaptation to stress and Stress management
Responses to stress include adaptation, psychological coping such as stress management, anxiety, and depression. Over the long term, distress can lead to diminished health or illness; to avoid this, stress must be managed.

General Adaptation Syndrome
This is a model on stress, researched mainly by Hans Selye on rats and other animals. His research involved exposing animals to unpleasant or harmful stimuli such as injections, extreme cold and even vivisection.

He found that all animals showed a very similar series of reactions, broken into three stages. He describes this universal response to the stressors as the General Adaptation Syndrome or GAS in 1956.

Stage one: alarm
When the threat or stressor is identified or realised, the body's stress response is a state of alarm. During this stage adrenaline will be produced in order to bring about the fight-or-flight response. There is also some activation of the HPA axis, producing cortisol.

Stage two: resistance
If the stressor persists, it becomes necessary to attempt some means of coping with the stress. Although the body begins to try to adapt to the strains or demands of the environment, the body cannot keep this up indefinitely, so its resources are gradually depleted.

Stage three: exhaustion
In the final stage in the GAS model, all the body's resources are eventually depleted and the body is unable to maintain normal function. At this point the initial autonomic nervous system symptoms may reappear (sweating, raised heart rate etc.). If stage three is extended, long term damage may result as the capacity of glands, especially the adrenal gland, and the immune system is exhausted and function is impaired resulting in decompensation. The result can manifest itself in obvious illnesses such as ulcers, depression or even cardiovascular problems, along with other mental illnesses.

Neuro-chemistry and physiology
The neurochemistry of the general adaptation syndrome is now believed to be well understood, although much remains to be discovered about how this system interacts with others in the brain and elsewhere in the body. 
The body reacts to stress first by releasing the catecholamine hormones, epinephrine and norepinephrine, and the glucocorticoid hormones, cortisol and cortisone.

Stress activates the sympathetic branch of the autonomous nervous system and produces the fight-or-flight response, causing the body to divert bloodflow to large muscles as the body prepares to run away from or fight something. Less blood flows to the digestive system and other organs that do not assist in fleeing or fighting, producing dry mouth, motor agitation, sweating, pallor, enlarged pupils and over the long term, insomnia. Modern stressors can cause continual sympathetic nervous system activation with very little opportunity for the parasympathetic nervous system to activate. When the parasympathetic system is active, the bowel and other non-muscle organs receive good blood-flow, the pupils constrict, and the glands all function well and secrete their various compounds. Absence of the autonomic parasympathetic activation leads to poor digestion and may lead to poor healing and organ function.[citation needed]

The hypothalamic-pituitary-adrenal axis (HPA) is a major part of the neuroendocrine system, involving the interactions of the hypothalamus, the pituitary gland, and the adrenal glands. The HPA axis is believed to play a primary role in the body's reactions to stress by balancing hormone releases from the adrenaline-producing adrenal medulla, and from the corticosteroid-producing adrenal cortex. Stress can significantly affect many of the body's immune systems, as can an individual's perceptions of, and reactions to, stress. The term psychoneuroimmunology is used to describe the interactions between the mental state, nervous and immune systems, as well as research on the interconnections of these systems.

Historical origins of the concept of stress
It was gradually realized that such concepts as anxiety, antagonism, exhaustion, frustration, distress, despair, overwork, pre-menstrual tension, over-focusing, confusion, mourning, and fear could all come together in a general broad term, stress. The popular use of the term in modern folklore expanded rapidly and created an industry of popular psychology, self-help, psychotherapy, and sometimes quackery. There were a series of films in the 1930s, 1940s, & 1950s that dealt with mad scientists playing with hormones that seem related to this folklore.

The use of the term stress in serious and recognized cases, such as those of post-traumatic stress disorder and psychosomatic illness, has scarcely helped clear analysis of the generalized "stress" phenomenon. Nonetheless, some varieties of stress from negative life events (distress) and from positive life events (eustress) can clearly have a serious physical impact distinct from the troubles of what psychotherapists call the "worried well."

Stress and illness
In a review of the scientific literature on the relationship between stress and 4 well-known diseases, the authors found that stress plays a role in triggering or worsening depression and cardiovascular disease and in speeding the progression of HIV/AIDS, and commented that additional studies across a broader range of cancers are needed before fairly evaluating the role of stress in cancer".

Burnout (psychology)
Burnout is the emotional exhaustion in the work arena associated with chronic dis-stress leading to a depletion of resources, emotional and mental fatigue. Burnout can be alleviated or averted through the use of stress management.[citation needed] Eustress, by definition, can not lead to burnout.

Burnout itself has been linked to the development of diabetes, with a prospective study of 677 employed men and women finding that after a 3 to 5 year follow up, burnout resulted in a 1.84-fold increased risk of diabetes even after adjusting for confounding factors, and 4.32-fold increase in a subsample of 507 workers after additional control for blood pressure levels.

Common factors of stress
Both negative and positive stressors can lead to stress. Some common categories and examples of stressors include:

Sensory: pain, bright light
Life events: birth and deaths, marriage, and divorce
Responsibilities: lack of money, unemployment
Work/study: exams, project deadlines, and group projects
Personal relationships: conflict, deception
Lifestyle: heavy drinking, insufficient sleep, Caring too much
Early life exposure (e.g. child abuse) can permanently alter an individual's stress response[citation needed]
Environmental: Lack of control over environmental circumstances, such as food, housing, health, freedom, or mobility
Social: Struggles with conspecific individuals and social defeat can be potent sources of chronic stresses.

Stress is difficult for scientists to define because it is a subjective sensation associated with varied symptoms that differ for each of us. In addition, stress is not always a synonym for distress. Situations like a steep roller coaster ride that cause fear and anxiety for some can prove highly pleasurable for others. Winning a race or election may be more stressful than losing but this is good stress.

Increased stress increases productivity – up to a point, after which things rapidly deteriorate, and that level also differs for each of us. It’s much like the stress or tension on a violin string. Not enough produces a dull raspy sound and too much an irritating screech or snaps the string – but just the correct degree of stress creates a beautiful tone.

Similarly, we all have to find the right amount of stress that permits us to make pleasant music in our daily lives. You can learn how to utilize and transform stress so that it will make you more productive and less self-destructive.

-Paul J. Rosch, M.D., F.A.C.P.
President, The American Institute of Stress Clinical Professor of Medicine and Psychiatry  New York Medical College 
Honorary Vice-President, International Stress Management Association