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In a recent study, childhood physical abuse increased the risk of developing cancer by 40%. What are the potential mechanisms? Here are my thoughts:
Traumatic events such as childhood physical abuse may lead to chronic hypothalamic-pituitary-adrenal dysregulation with low cortisol production. This is seen particularly in those suffering from posttraumatic stress disorder or anxiety disorders resulting from childhood abuse.
Impaired adrenal cortical response to stress may lead to a chronically elevated stress signaling, as cortisol helps reduce norepinephrine signaling. Norepinephrine is the most prominent signal for stress.
Increases in norepinephrine signaling lead to insulin resistance. Insulin resistance leads to an increase in insulin production to maintain glucose control and glucose entry into cells. Insulin, however, stimulates cellular growth. Chronically high levels of insulin increases the risk for cancer.
Increases stress signaling may lead to an increase in pro-inflammatory cytokine signaling from brain microglia. The increase in pro-inflammatory cytokine signaling as well as increase norepinephrine signaling increases immune system activity and inflammatory processes. The increase in inflammatory processes may increase oxidative stress which may lead to damage of DNA and cancer.
Childhood abuse also leads to the development of maladaptive or poorly developed mindfulness, distress tolerance, self-nurturing, problem-solving, and relationship skills. Childhood abuse also may disrupt or warp the development of a person’s belief system – the internal analog/model of reality through which the brain filters new sensory input. Objects or persons in the abused person’s environment may have higher perceived threats to self than those in non-abused persons. This may lead to chronically stressful interactions with objects or persons in the environment. Traumatic memories may provide a constant source of stress. One of cortisol’s functions is to enable the brain to ignore distracting emotionally negative memories. But impaired production of cortisol promotes flashbacks instead – since these distressing memories cannot be suppressed or ignored without adequate cortisol production. The sum of these psychological deficits is chronically increased stress signaling and the above-fore-mentioned risks for cancer.
There are severe other mechanisms involved as we go deeper into the biochemistry of the stress response. But the above are a few ideas.
Medline: http://www.ncbi.nlm.nih.gov/pubmed/19472404?
Cancer. 2009 May 26.
Making a link between childhood physical abuse and cancer: results from a regional representative survey.
Fuller-Thomson E, Brennenstuhl S.
Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.BACKGROUND:: Abuse in childhood is associated with many negative adult health outcomes. Only 1 study to date has found an association between childhood abuse and cancer. By using a regionally representative community sample, this preliminary study sought to investigate the association between childhood physical abuse and cancer while controlling for 3 clusters of risk factors: childhood stressors, adult health behaviors, and adult socioeconomic status.
METHODS:: Regional data from the Canadian provinces of Manitoba and Saskatchewan were selected from the 2005 Canadian Community Health Survey. Of the 13,092 respondents, 7.4% (n = 1025) reported that they had been physically abused as a child by someone close to them, and 5.7% (95% confidence interval [CI], 4.9-6.6) reported that they had been diagnosed with cancer by a health professional. The regional level response rate was 84%.
RESULTS:: Childhood physical abuse was associated with 49% higher odds (95% CI, 1.10-2.01) of cancer when adjusting for age, sex, and race only. The odds ratio decreased only slightly to 47% higher odds (95% CI, 1.05-1.99) when the model was adjusted for all 3 clusters of risk factors.
CONCLUSIONS:: A significant and highly stable association between childhood physical abuse and cancer was found even when adjusting for 3 clusters of risk factors. Further research focusing on the potential mechanisms linking childhood abuse and cancer is needed. Cancer 2009. (c) 2009 American Cancer Society.
PMID: 19472404 [PubMed – as supplied by publisher]
This is great information! Understanding the education of how the development of the brain as a child works, is so crucial I believe. Each time a child occurs trauma, I understand it as the brain suffers a particular change in the prefrontal cortex, the cerebellum and the limbic system.
Do you think the ongoing stress raises levels of the “fight or flight” hormone cortisol, which may suppress the immune system’s ability to detect and destroy cancer cells?
@shan_e_wilson 331 wrote:
This is great information! Understanding the education of how the development of the brain as a child works, is so crucial I believe. Each time a child occurs trauma, I understand it as the brain suffers a particular change in the prefrontal cortex, the cerebellum and the limbic system.
Do you think the ongoing stress raises levels of the “fight or flight” hormone cortisol, which may suppress the immune system’s ability to detect and destroy cancer cells?
I generally don’t believe the ongoing stress raises cortisol production. I take care of a lot of children in my practice, many of whom have been abused. I never see high cortisol levels.
What is interesting about the literature on stress and adrenal function is that often cited are high cortisol levels causing problems. The problem is that in real life, I very rarely see a high cortisol level. Whenever a study is done in-vivo, it uses supraphysiologic doses of cortisol to demonstrate the toxicity of cortisol. The problem I have is that I don’t see supraphysiologic levels of cortisol unless the person has Cushing’s syndrome.
Whenever I do see a high cortisol level, it is in a person who has high stress levels. But this high cortisol level is a physiologic and appropriate response to the stress. Cortisol at physiologic levels is protective in function.
Note that the reference range for Cortisol has certain assumptions. The person is at rest, without excessive stress, without recent excessive exercise. The person should not work out heavily the day before the test. When these assumptions are not met, then the reference range needs to be shifted. When a person is under high stress, the physiologic range is going to be higher than a person at rest, under minimum stress.
Cortisol is the primary anti-stress response signal. In the brain, it helps improve focus so that distracting emotional information does not detract from what the person is trying to accomplish. It helps reduce destruction from excessive inflammatory activities of the immune system. And so on.
Think about it. Frequently, athletes, after a work out or after a game or even before a game, take Ibuprofen to help reduce the aches and pains from the physical exertion. What did they just do? They are reducing the inflammatory processes that occur with the stress of physical exertion. This helps them recover better. This use of Ibuprofen, however, is exactly what cortisol is suppose to be doing though using a difference mechanism of action. They are augmenting the effects of cortisol.
As I note above, it is the inability to produce cortisol appropriately in response to stress that causes problems. When the body produces cortisol appropriately at high physiologic levels in response to stress, they are protected from the damage of that stress. You seldom see children with cancer. But when cortisol goes down, they are in trouble. This is what happens over time. People with posttraumatic stress disorder – and childhood abuse is a traumatic event – produce too little cortisol. This is when you see the higher risk for cancer.
Dr. Mariano,
Thank you for taking the time to write this post. It was very educational and enlightening.
Another thing I was pondering..was how childhood trauma can impact gene expression and DNA polymorphism through alterations in methylation.
@shan_e_wilson 339 wrote:
Another thing I was pondering..was how childhood trauma can impact gene expression and DNA polymorphism through alterations in methylation.
Methylation reactions are part of 1-carbon metabolic pathways involving Folic Acid, Vitamin B12, and Iron, among other nutrients. These are involved in DNA/RNA synthesis and Protein Synthesis (including enzymes), as well as the production of Neurotransmitters/signals such as Serotonin, Norepinephrine and Dopamine.
In relating these metabolic processes to childhood trauma, the cogent point would be: what happens to a person who is traumatized in childhood in regard to socioeconomic status and nutrition.
When a person has experienced childhood trauma, there is a good chance they develop seriously flawed belief systems – my own term for their internal representation of reality. And they will develop flawed adaptive behavioral skills. With childhood trauma, the person may develop a negative sense of self, distrust of others, a foreshortened view of what they may accomplish in life. The person may have poor skills in mindfulness, self-nurturing, distress tolerance, problem solving, relationships.
Such a person would be at high risk of having a poor education. Such a person may be at high risk of being unemployable or having limited work skills and job opportunities. Such a person would be at risk for depending on drugs since they don’t have adequate self-nurturing skills. Such persons are at risk of developing unstable, stressful, and poor relationships. Such persons are at risk of living at a low socioeconomic level. Such persons are at high risk of being traumatized again or of living with daily traumatizing stress – as do people who live in poverty. Such a person is at risk of developing mental illness. Mental illness means such persons also tend to have multiple medical problems such as heart disease, diabetes, asthma, arthritis, hypertension, stroke, cancer. If they are working, a large part of their income is spent on medical care. Such a person is at risk of legal problems and incarceration. It is well known, for example, that 90% or more of men in prison have been abused as children.
Now what chance does such a person have of having good nutrition? Poor most of the time.
When one is not affluent, one can’t purchase meats. One is more likely to eat junk food. One is more likely to eat primarily carbohydrates such as breads, cereals, various junk foods. These are much less expensive that the more nutritious foods. One is less likely to purchase supplements for the nutrients that are missing in modern foods.
With poor nutrition, impaired 1-carbon metabolism – including methylation is likely.
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