Chronic Stress Empowering Cancer

Chronic Stress Empowering Cancer

Anne M. Shelton

Saybrook University

Abstract

The author has survived over four cancers and has a mission to understand psychophysiological factors that may help prevent cancer regeneration and development. Stress appears to manipulate a person’s homeostasis by altering cells and influencing a malfunction on genes. The body’s response to chronic stress is a psychophysiological phenomenon causing a weakened immune system. The weakened immune system leads to a discord of cell regeneration, growth, and eradication. Cancer cells appear to become empowered to manifest beyond their micro-environment as a result. 

Chronic Stress Empowering Cancer

             Several animal and human studies have suggested a link to cancer and stress (Moreno-Smith et al., 2010). According to Moreno-Smith et al. (2010), well documented impact of stress on the immune system may give relative insight on the potential effects of stress on cancer related genes and empowering them to metastasis. It is hypothesized that more than one gene or cell is influenced by the manipulation of stress. Research has shown there to be a detrimental impact on cell proliferation when there is a continuous discombobulation in the delicacy of the body’s balance. The human psychophysiology ability to maintain homeostasis easily may be altered or defeated from psychological stress.

The Immune System Under Stress

                The immune system has numerous defenses to protect the body by eliminating pre-cancerous cells (Soung & Kim, 2015).  According to Soung and Kim (2015), studies involving humans and animals have suggest natural killing cells are vital in the eradication of metastatic tumor cells. The natural killer cells may receive mixed signals and/or lack the efficacy in functioning which ultimately may lead to a metastatic cancer. According to Zakiryanova et al. (2018), systemic immune dysregulation and suppression are associated with tumor progression and development. How the tumor forms in a micro-environment, growth, and metastasis is all dependent on the mechanisms of the immune system (Zakiryanova et al., 2018).

               According to Zakiryanova et al. (2018), immune abnormalities are often contributed to stress-induced alterations.When the human body is faced with stress, a “flight or fight” response is initiated (Segerstrom & Miller, 2004). Segerstrom and Miller (2004) explains the response triggers the hypothalamic pituitary adrenal (HPA) axis and SNS in excreting cortisol, norepinephrine, and epinephrine.   The amount of protein that is vital to alert immune fighting lymphocytes is reduced from excreting cortisol.  This is the body’s physiological mechanism of survival that leads to a disruption of the regulatory effects and function of the immune system. Numerous studies have suggested stress is disruptive to the neuroendocrine circadian rhythm favoring metastasis and tumor growth (Moreno-Smith et al., 2010). According to Flores, et al. (2017), hormone levels can adversly be altered from chronic stress. 

                When a person is undergoing stressful experiences that become chronic, research has suggested the circadian rhythm of the HPA axis to be disrupted (Soung & Kim, 2015). Sephton and Spiegel (2003) explains the stressful disruption of the HPA axis and hormone alterations influence cancer growth. Individuals with a high risk of breast cancer and poor prognosis were observed to have an abnormal circadian rhythm, low activity and number of normal killing cells, and increased mortality for up to seven years post assessment. According to Soung and Kim (2015), the HPA axis dysfunction was affliated with poor sleep, mutations of the circadian clock genes, and prior marriage disruption. The overall impact effects the body’s physiological regulation contributing to a progression of diseases, including cancer (Flores et al., 2017).  

              Soung and Kim’s (2015) research in animal studies suggest the SNS and HPA axis resulting in immune alterations from stress most likely to lead to impacting factors that contribute to mortality and morbidity associated with cancer. Soung and Kim (2015) explains a particular study in mice showed tumor growth to increase and progress when they were exposed to a variety of different stressors. A decrease was seen in immune cells that included suppressor T cells and a reduction of cytokine/ chemokine secretion. Relatively to breast cancer metastasis to lung cancer showed and increase in b-adrenergic antagonists and agonists (Soung & Kim, 2015). 

Dopamine

              Dopamine is a vital neurotransmitter in the brain that facilitates coping with stress (Tilan & Kitlinska, 2010). According to Moreno-Smith et al. (2010), the body increases dopamine after the release of cortisol, epinephrine and norepinephrine in acute stress. In chronic stress the body has a decrease release of dopamine that ultimately decreases the dopamine level (Moreno-Smith et al., 2010). Moreno-Smith et al. (2010) summarizes dopamine has influence to impede tumor growth by discouraging angiogenesis.  Moreno-Smith et al. (2010) research suggested dopamine has potential to have an indirect or direct response on the immune system. 

               Moreno-Smith et al. (2010) research demonstrated that the dopamine therapy counteracted stimulatory effects of norepinephrine on ovarian-stressed cancer mice with tumor growths. The study suggests dopamine to be implicated has a potential strategy in blocking the detrimental effects from chronic stress. Tumor growth in mice has shown to be promoted by a depletion of dopamine that minimizes response of the lymphocytes from the thymus gland (T) cell. T cells express dopamine receptors which suggests possibility for dopamine to play a role in immune regulation (Moreno-Smith et al., 2010).  Tilan and Kitlinska (2010) experiment showed mice associated with high levels of dopamine had reduced growth in Lewis lung carcinoma. Furthermore, endogenous levels of dopamine in gastric cancer were much lower than in healthy tissue. This indicates neurotransmitters may act as tumor suppressants (Tilan & Kitlinska, 2010).

Stress and DNA

               Carcinogens have capability to damage DNA creating mutant cells; a healthy functioning immune system has enzymes able to destruct or repair the DNA cells (Soung & Kim, 2015). Soung and Kim (2015) explains when the immune system is unable to make the progress of terminating or reconstructing, cancer risk becomes increased. According to Soung and Kim (2015), the physiological changes triggered by carcinogenic stress alter the body’s physiological mechanism in DNA repair. Soung and Kim (2015) research suggested a reduction of DNA repair was found in humans with psychiatric illnesses. This suggest an influence of psychological factors and the cancer process may be intercorrelated.

             When DNA is damaged the tumor suppressor protein p53 that faciliates vital cellular function is often mutated (Flint & Bovbjerg, 2012). Flint and Bovbjerg (2012) study in breast cancer patients discovered the protein to be downregulated or inactivated. According to Flint and Bovbjerg (2012), stress hormones inducing damage to DNA sensors MDM2, Chk1, Chk2, and protooncogene CDC25A. The protooncogene CDC25A following DNA damage results in an increase of cell transformation (Flint & Bovbjerg, 2012).  

             The protooncogenes are regular genes affiliated with cell growth, differentiation, apoptosis and proliferation (Zakiryanova et al., 2018). Zakiryanova et al.(2018) explains when the gene becomes overexpressed or mutated they can trigger normal cells to involve into cancer. 

According to Zakiryanova et al. (2018), the protooncogene has been expressed in the immune system, including all cells. Impacts of the immunse system may be linked to the oncogene signaling system which may suggest cancer-associated with immune system dysfunction is an effect of the oncogene. This theory may suggests a weakend or malfunctioning immune system from stress may cause the oncogene to manifest into cancer. 

             The Myc gene is a particular photooncogene that is also involved in pathophysiological and physiological pathways (Zakiryanova et al., 2018). According to Zakiryanova et al. (2018), the Myc gene is helps regulate the development of immune diseases including activation and differentiaion in immune cell development and post stimulation. Zakiryanova et al. (2018) explains a hallmark of cancer is metabolic reprogramming. Myc is a valuable coordinator in T-cell activation-induced growth, metabolic programming and proliferation of cells. 

                                                             ATF3 Gene

              Genes carry instructions on protein, cancer-inducing genes may cause an increase production of protein that facilitate cell growth. According to Paddock (2013), research has suggest when the body is enduring stressful physiological conditions that are threatening homeostasis the ATF3 gene becomes activated.  Hai et al. (1999) study suggest ATF3 to be diverse in its expression in any kind of tissue or certain time when responding to extracellular stress signals. The ATF3 gene encodes cAMP which is a responsive binding protein of the ATF/CREB family (Liang, Wolfganf, Chen, Chen, & Hai, 1996). Moreno-Smith et al. (2010) explains the binding is a critical factor that is activated by multiple signals responsing to stress hormones and external stimuli. 

               Accoring to Paddock (2013), the activation of ATF3 under normal circumstances protects the body by initiating cells to self-destruct that have become permanently damaged from a lack of oxygen or irradiation caused by stressful conditions.  The growth of tumors at a primary site is dependent on oxygen diffusion and nutrients.  Metastatic sites are dependent on receiving a balance of negative and positive signals from the endocrine pathways that are influencial for tumor cell regeneration and growth (Moreno-Smith et al., 2010).

             The ATF3 gene induction is part of a cellular response to stress (Hai et al., 1999). 

 Ohio State University did a study that suggested cancer cells had the ability in tumor sites to turn on ATF3 in immune cells (Paddock, 2013). Paddock (2013) explains the correlation resulted ATF3 to trigger a malfunction in the immune cells which caused cancer cells to expand beyond a tumor to other parts of the body.  Physiological stressors engaging in the ATF3 gene suggest an imperative role in stress response. 

               According to Paddock (2013), a breast cancer research was conducted using two different categories of mice. Group A was normal mice and group B was mice who had no cell ability to express ATF3. Both groups of mice were injected with breast cancer cells. Group A showed breast cancer spread more extensively and rapidly in the lungs than the group B mice that had no ATF3. Paddock (2013) research concludes to identify ATF3 as a director enhancing the metastasis of breast cancer. 

Stress-Reducing Cancer Intervention

                 A human study was conducted for stress-reducing interventions that involved a controlled group and intervention group who had stage one or two of malignant melanoma (Soung & Kim, 2015). Soung and Kim (2005) explains the intervention group that had not received any treatment post a surgical excision of the melanoma had shown a very significant relationship of minimized psychological distress. This group also had an increase in cytotoxicity of natural killing cells compared to the controlled group. In a six-year follow up of the patients, a significant decrease in mortality and recurrence was seen in the intervention group verse the controlled group. 

              According to Soung and Kim (2005), results were consistent with another intervention study involving self-hypnosis extending life in woman who had metastatic breast cancer. Spiegel, Bloom, Kraemer, and Gottheil (1989) study involved eighty-six patients with metastic breast cancer. Fifty of the patients were in the self-hypnosis intervention group that lasted one year and thirty-six were in the controlled group that only received oncological care (Spiegel et al., 1989). Spiegel et al. (1989) explains the study was followed up ten years later and showed only three patients living. Death records were obtained and results revealed from the time of participant selection the average months lived by the intervention group was thirty-seven months and the controlled group eighteen months. Spiegel et al. (1989) research indicated divergence in survival happened eight months after intervention ended.

Discussion

              Chronic stress appears through research to cause a psychophysiological dysfunction in the body’s homeostasis impacting the immune system and cell function. The dysregulation causes the cells to receive mixed signals. Induced by cell confusion and defeat, a chain reaction appears to manipulate genes capable of manifesting into cancer beyond its microenvironment. Stress empowers the cancer genes to regenerate and grow. 

                Implications for psychological interventions to help a person de-stress, cope and manage their environment may be well worth exploring to prevent cancer from manifesting or reoccurring. Psychological interventions  may encourage survival and immune function in cancer patients. If stress is an inducer, clearly destressors are worth exploring to facilitate treatment. Indentifying genes that are impacted by emotional alterations may bring light in discovering other anticancer treatment and drugs affiliated with stress and psychological disorders.

Shelton, A. (2019, July 24). Chronic Stress Empowering Cancer. Saybrook University.

  

References

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