Psychogenic Carcinogenesis

Field: Medicine (Health Sciences)

Scientific advances in understanding the cellular-molecular-genetic mechanisms of carcinogenesis (Coleman et al., 2006;Finn, 2008) and the impressive advances in the treatment of cancer in animal models clearly not correspond to the results of clinical studies (Knight et al., 2006).Cancer process is still uncontrollable and global forecasts are disappointing: in the world by 2050 will increase from 11 up to 24 million new cases and death rate -from 6 (in 1999) up to 16 million (Boyle et al., 2005).In addition, despite enormous progress in understanding biology of malignant tumors and mechanisms of carcinogenesis, the constant improvement of malignant tumor treatment methods the five years' survival rate of cancer patients has increased only by 14% -from 50% up to 64% over the past 30 years (Herbst et al., 2006).Obviously, there is a large gap between the cancer science and clinical oncology practice and it is constantly increasing as the molecular-genetic research technologies develop which lead scientists from a holistic vision of the person.Now considering the problem of cancer from the standpoint of experimental animal models and the three officially accepted types of carcinogenesis (chemical, physical & biological) is not enough.We believe that there is the fourth type of carcinogenesis -psychogenic carcinogenesis (Bukhtoyarov & Samarin, 2009) the idea of the existence was generated during the clinical work with cancer patients.Thus, the multicenter anamnestic study of causes of cancer among 1200 cancer patients with 23 kinds of cancer from three regions of Russia and Kazakhstan showed that 50%-70% of cancer patients were determined by psychogenic factors (death of the close person, divorce, frequent family conflicts, change of residence, appearance of the disabled in family etc.), as the major ones in the appearance of malignant tumors (Bukhtoyarov & Arkhangelskiy, 2008).Understanding of psychogenic carcinogenesis would allow to find the new ways to solve many problems in modern oncology and to form the holistic approach to the cancer problem. Psychogenic carcinogenesis: A new look at old problemsAt present, a huge number of various scientific and clinical evidence was accumulated that can not be explained in terms of the existing views on the mechanisms of carcinogenesis.However, these facts can be explained by the pathogenetically meaningful participation of the psyche in the appearance, progression and recurrence of cancer.Ignoring this understanding explains much of uncontrollability and unpredictability of the flow of the cancer process in some cancer patients, and also explains the considerable difficulties in www.intechopen.comAdvances in Cancer Management 18 creating effective anti-cancer drugs.The main factor triggering the activation mechanisms of psychogenic carcinogenesis is a chronic debilitating psycho-emotional stress (CPS). Chronic psycho-emotional stress and carcinogenesisIt is known that two interconnected processes are necessary for developing of a cancer under influence of chemical, physical or biological carcinogenic factors: genetic break/cell DNA damage and compromising of the immune system.However, these pathological processes can be generated without participation of exogenous carcinogens, i.e. can be induced psychogenically.Chronic psycho-emotional stress is capable to activate key carcinogenic mechanisms and to induce malignant tumor growth. Chronic psycho-emotional stress and DNA damageIt is known that CPS leads to dysfunction of telomere (the ends of chromosomes) and to reduction of their length (Epel et al., 2004;Arehart-Treichel, 2005), which is accompanied by genome instability, acceleration of biological ageing (Simon et al., 2006), reduction of life expectancy (Kimura et al., 2008), formation of a lot of diseases including cardiovascular diseases and cancer (Anisimov, 2007).Short telomeres are biomarkers of cell ageing; they specify stressful history of a cell and cumulative action of a high level of oxidant stress on a cell (von Zglinicki & Martin-Ruiz, 2005).In its turn oxidant stress is capable to be activated in reply to CPS and damage DNA, lead to gene mutations by means of reactive oxygen and nitrogen species (RONS) that becomes critical event in activation of key tumorogenesis mechanisms (Gidron et al., 2006;Halliwell, 2007;Toyokuni, 2008).Person in condition of CPS is very sensitive to damaging action of various mutagens, spontaneous and induced levels of damage of DNA are more often registered (Dimitroglou et al., 2003).The chronic stress in model in vivo facilitates development of skin cancer almost in 3 times on a background of carcinogenic action of ultra-violet irradiation (Saul et al., 2006). Chronic psycho-emotional stress and compromised immunityGenetic damages are necessary but insufficient for the neoplastic transformation of the cells and tumor growth, cancer progressing or relapse as formation of tumor is impossible without infringements in immune system where stressful factors and mentality take an active part (Schussler & Schubert, 2001), that is a subject of studies psychoneuroimmunology and its sub-discipline -psychoimmunology of cancer (Lewis et al., 2002).On background of CPS decreased hypothalamo-pituitary-adrenal (HPA) and sympatheticadrenal-medullary (SAM) axes responsiveness is observed that is accompanied with disregulation of neuromediator systems, infringement of hormonal expression and functions of immune system (Reiche et al., 2005;Ostrander et al., 2006).At the cellular level stressed and depressed patients had overall leukocytosis, high concentration of circulating neutrophils, reduced mitogen-stimulated lymphocyte proliferation and neutrophil phagocytosis.At the molecular level high levels of serum basal cortisol, acute phase proteins, chemokines, adhesion molecules, plasma concentration of interleukins IL-1, IL-6, and TNF-alpha and a shift in the balance of Th1 and Th2 immune response towards humoral immunity.Both stress and depression were associated with the decreased cytotoxic T-lymphocytes and natural killer cell activities affecting the processes of the immune surveillance of tumors, the accumulation of somatic mutations and genomic instability.DNA damage, growth and angiogenic factors, proteases, matrix metalloproteinases and reactive www.intechopen.com