Cancer and stressors
An estimate of cancer prevalence in US by American cancer society goes to 11,028,000. There are different PSs related to cancer at different time points starting from the prognosis of the cancer, continuing through the course of cancer treatment, after the therapy and beyond. So far, most of the studies that have been done are related to breast cancer among female population belonging to different age groups, different regional and social backgrounds as well as different social status (22). The reported stressors associated with women breast cancer include social stressors due to the difficulty in dealing with the society as well as adjusting in the social group after disease prognosis, peer pressure where especially women undergoing cancer treatment show increased level of anxiety and stress due to either lack of support or increased sense of dependence on their partners during the course of disease (23). Emotional stressors are another kind of stressors that accompany breast cancer and include various emotional experiences after cancer prognosis or related to treatment techniques or therapies they undergo. These stressors intensify during the course of disease. A detailed study by Silvia Schmid-Buchi et al discusses about the various emotional and social distresses associated with breast cancer patients as well as their relatives post-treatment. (24) Thus, as far as breast cancer is concerned women are susceptible to different kind of stressors which have been independently studied. Henceforth, two main reasons for breast cancer being the major theme of study by different research groups can be a) breast cancer is the second most prevalent forms of cancer worldwide and there are a good number of studies which establish different stressed states associated with cancer; b) diversity of stressors related to a breast cancer patient provides a greater scope to study the affect of different kind of stressors for a single disease condition. Thus, breast cancer has more or less become a model for stress related studies in human population. An account of breast cancer related studies asserts that while variability in certain factors like age group doesn’t significantly affect the stress-disease correlation, other factors like different regional and social backgrounds as well as different social status showed significant affects on disease progression. This can be justified as the latter factors may influence the psychological state of a person more significantly unlike former. A set of studies done by Alice et al. support that those cancer patients which belong to lower socioeconomic backgrounds have poorer adjustment to cancer which further relates to social stressor This is also true for patients with prostate and colorectal cancer. (22) Thus, this very basic study gives a first idea of psychological factors associated with cancer. All the recent studies further reviewed here show a dependence of cancer progression on stress established on the basis of positive effects of various psychological interventions in cancer recovery and survivability. The studies where stress among the breast cancer patients is relieved by various psychological interventions provided in the form of different programs like mindfulness based stress reduction program (MBSR) or cognitive behavioral stress management intervention (CBSM) especially after the primary cancer treatment not only show better coping to the stress, improved quality of life (QOL), reduced anxiety symptoms, reduced negative affects and a positive attitude for life but also show better recovery rates and lowered probability of cancer recurrence. (25-27) Biological marker that was used to monitor stressed and non-stressed states was cortisol and showed reduction in serum levels immediately after these psychological interventions. In these studies it has been shown that these psychological interventions mediate the immune system in a positive way which give better resistance to cancer and reduce its chances of recurrence.
According to set of experiments performed on breast cancer patients after they underwent primary cancer treatment viz. surgery, Antoni et al showed that CBSM buffers the adjuvant therapy by increasing the production of Th1 cytokines, IL2 and IFN-γ in PBMC of patients that were a part of intervention unlike patients which were not. The “buffering” action of CBSM was deduced from the fact that during a 12 month follow up, the levels of all the cytokines mentioned above stayed elevated only for a 6 month period, the duration for which adjuvant therapy was given. Moreover, women assigned to CBSM also showed greater cellular immune function deduced from in vitro studies on lymphocyte proliferation responses to anti-CD3 stimulation at 3 month follow up which can be linked to changes in Th1 and Th2 cytokine regulation as stated by some groups. (26, 28) In fact, it has been suggested that cell mediated immune indices may be the most sensitive to the stress-reducing effects of these interventions based on the studies of three groups. (26, 29-31) But again it becomes important to consider that the observed increased lymphocyte proliferative response after CBSM intervention can just be modulating system as stated by Mc Gregor et alinterpreted from experimental conditions. Hence, it still needs to be established that whether the observed changes in immune system are simply buffering effects or de novoactivation of some immune pathways irrespective of external therapeutics administered. The non-randomized controlled design study to evaluate the effects of MBSR (27) also showed similar kind of modulator results on immune system. The most important consequences of MBSR has been observation of the temporal sequence of activation of various cytokines starting from cortisol release and followed by IL-4, IL-10 production preceding IFN-γ and NKCC activity suppression which may indicate the plausible pathway of stress mediation. As the study used non-randomized group of people, a piece of argument can be easily framed against the reliability of the study. But since the above mentioned CBSM studies done on randomized group also account for stress relief, the results related to MBSR in cancer patients can be relied upon. The effect of social stressors was elucidated by studies (24) where effected women were assigned to weekly support groups, which emphasized on building strong supportive bonds, encouraging emotional expressions, dealing directly with fears of dying and death, reordering life priorities, improving relationships with family and friends, enhancing communication and shared problem solving with physicians and learning self hypnosis to control pain. It was found that at a 10 year follow-up, there was a statistically significant survival advantage for women in the group therapy. On average it increased the life expectancy with improved quality of life (QOL) for 18 months. Similar studies on group of patients suffering from melanoma as well as leukemia and lymphoma showed similar responses to psychosocial support.
Another kind of studies relate hypnosis and cancer where patients undergoing cancer chemotherapy duly attended psychological interventions consisting of training in progressive muscular relaxation and cue controlled relaxation, direct hypnotic suggestion and a new procedure called nausea management training. The new thing about this study was that the improved conditions in the diseased state was attributed to more regularity and willingness to receive chemotherapy due to reduced side effects like vomiting, nausea and better control over them through nausea management training rather than neuroendocrine regulation. The psychological interventions seemed to have prophylactic effects. Another important outcome of the study was establishment of enhanced lymphocyte responsiveness and IL-1 with increased Creative Imagination Scale Scores in experimental group in reference to control group. A very important immunologic factor that has been linked with cancer progression and metastasis is Natural killer cell cytotoxicity (NKCC). Anderson et al have come up with an important finding that high distress in newly diagnosed breast cancer patients not only shows lower T cell proliferation in response to anti-CD3 stimulation in vitro but also have a lower NKCC with or without IFN-γ activation. (29, 30) Though it is difficult to state at this point of time that what factor in psychological interventions viz. reduced anxiety, better stress management skills , better coping skills or being in a supportive group is the most influencing of all on immune systems, it is clear that interventions can manipulate physiological systems. Similarly, the mechanisms by which these psychological interventions affect the immune system have not been pin pointed yet. Rather there are a number of proposed mechanisms based on the studies above (Figure 1). One of the mechanisms as proposed by Antoni et al (25) states that increased glucocortcoid levels in synergism with catecholamines, which also show increased levels of expression in a stressed state, facilitates the cancer growth through various glucocorticoid receptor mediated activation or repression of target genes. Increased level of glucocorticoid is known to down-regulate cellular immune responses. It also affects the transcription of many cytokines like IL-2 and INF-γ which has a stimulatory effect on NK cytotoxicity as well as lymphokine activated killer cells. These inhibitory effects can be further related with the down-regulation of IL-12 receptor on these cells as well as through down-regulation of the surface expression and function of triggering receptors involved in NK cell cytotoxicity. As both of the biomolecules are a part of neuroendocrine and Sympathetic nervous system respectively, this implies the involvement of both these systems in response to stress condition in coordination with the limbic system.
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