Stress and cancer
More details
Hide details
Department of Environmental Medicine and Epidemiology, Faculty of Medical Sciences, Medical University of Silesia, Katowice, Poland
High School of Strategic Planning, Dąbrowa Górnicza, Poland
Jadwiga Jolanta Jośko - Ochojska   

Katedra i Zakład Medycyny i Epidemiologii Środowiskowej, Wydział Nauk Medycznych, Śląski Uniwersytet Medyczny w Katowicach, ul. Jordana 19, 41-808 Zabrze, Polska
Ann. Acad. Med. Siles. 2020;74:166–180
Scientific research has shown that during stress, the secretion of hormones and neurotransmitters in the brain, etc. is definitely stronger and longer lasting when persons are convinced that they cannot cope with the requirements of a stressful situation, i.e. they are in a state of uncontrolled stress. The main indicator of this condition is a long-term increase in the concentration of stress hormones in the blood. The higher the catecholamine concentration, the more DNA damage, the more cells undergoing tumour transformation, the larger the tumour and the more advanced the disease. Catecholamines also narrow blood vessels, which leads to an increase in VEGF expression, responsible for an increase in angiogenesis, and hence tumour growth and tumour metastasis. Cortisol contributes to inhibition of the immune system and changes in the central nervous system. Under uncontrolled stress, telomeres are shortened, which is another reason for shortening life expectancy. It has also been proven that stress and trauma are inherited in subsequent generations in the mechanism of epigenetic inheritance. Despite epigenetic predispositions to develop various malignancies, including ovarian, stomach and colorectal cancer, people can move from uncontrolled to controlled stress in a particular situation, even though the situation itself does not change. This is a breakthrough message. During cancer, the transition to controlled stress definitely supports therapy, increasing your chances of survival or even recovery. The most common condition for taking control of stress is to change your current lifestyle.
Jośko-Ochojska J., Ochojski A. Rozmowy przy kawie. O stresie, lęku i traumie. Wydawnictwo Andrzej Ochojski. Rybnik 2019.
Mason J.W. A re-evaluation of the concept of `non-specifity' in stress theory. J. Psychiatr. Res. 1971; 8(3): 323–333, doi: 10.1016/0022-3956(71)90028-8.
Borczykowska-Rzepka M. Satysfakcja z życia matek dzieci z zaburzeniami ruchowymi pochodzenia ośrodkowego oraz dzieci z mózgowym porażeniem dziecięcym. Rozprawa doktorska. Śląski Uniwersytet Medyczny w Katowicach. Katowice 2008.
Winchester D.P. Breast cancer. PMPH-USA. 2006; 607: 3−4.
Lutgendorf S.K., Sood A.K. Biobehavioral factors and cancer progression: physiological pathways and mechanisms. Psychosom. Med. 2011; 73(9): 724−30, doi: 10.1097/PSY.0b013e318235be76.
Lillberg K., Verkasalo P.K., Kaprio J., Teppo L., Helenius H., Koskenvuo M. Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am. J. Epidemiol. 2003; 157(5): 415−423, doi: 10.1093/aje/kwg002.
Yang T., Qiao Y., Xiang S., Li W., Gan Y., Chen Y. Work stress and the risk of cancer: A meta‐analysis of observational studies. Int. J. Cancer 2019; 144(10): 2390−2400, doi: 10.1002/ijc.31955.
Al-Wadei H.A., Ullah M.F., Al-Wadei M.H. Intercepting neoplastic progression in lung malignancies via the beta adrenergic (β-AR) pathway: implications for anti-cancer drug targets. Pharmacol. Res. 2012; 66(1): 33−40, doi: 10.1016/j.phrs.2012.03.014.
Lee J.W., Shahzad M.M., Lin Y.G., Armaiz-Pena G., Mangala L.S., Han H.D., Kim H.S., Nam E.J., Jennings N.B., Halder J., Nick A.M., Stone R.L., Lu C., Lutgendorf S.K., Cole S.W., Lokshin A.E, Sood A.K. Surgical stress promotes tumor growth in ovarian carcinoma. Clin. Cancer Res. 2009; 15(8): 2695–2702, doi: 10.1158/1078-0432.CCR-08-2966.
Pu J., Bai D., Yang X., Lu X., Xu L., Lu J. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155. Biochem. Biophys. Res. Commun. 2012; 428(2): 210–215, doi: 10.1016/j.bbrc.2012.09.126.
Schuller H.M., Al-Wadei H.A., Ullah M.F., Plummer H.K. 3rd: Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. Carcinogenesis. 2012; 33(1): 191–196, doi: 10.1093/carcin/bgr251.
Wong H.P., Ho J.W., Koo M.W., Yu L., Wu W.K., Lam E.K., Tai E.K., Ko J.K., Shin V.Y., Chu K.M., Cho C.H. Effects of adrenaline in human colon adenocarcinoma HT-29 cells. Life Sci. 2011; 88(25-26): 1108–1112, doi: 10.1016/j.lfs.2011.04.007.
Chida Y., Hamer M., Wardle J., Steptoe A. Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat. Clin. Pract. Oncol. 2008; 5(8): 466–475, doi: 10.1038/ncponc1134.
Palm D., Lang K., Niggemann B., Drell T.L., Masur K., Zaenker K.S., Entschladen F. The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers. Int. J. Cancer 2006; 118(11): 2744–2749, doi: 10.1002/ijc.21723.
Armaiz-Pena G.N., Cole S.W., Lutgendorf S.K., Sood A.K. Neuroendocrine influences on cancer progression. Brain Behav. Immun. 2013; 30 Suppl(Suppl): S19–S25, doi: 10.1016/j.bbi.2012.06.005.
Surman M., Janik M.E. Stres i jego molekularne konsekwencje w rozwoju choroby nowotworowej. Postepy Hig. Med. Dosw. (online) 2017; 71(0): 485–499, doi: 10.5604/01.3001.0010.3830.
Flint M.S., Baum A., Episcopo B., Knickelbein K.Z., Liegey Dougall A.J., Chambers W.H., Jenkins F.J. Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts. Stress 2013; 16(1): 114–121, doi: 10.3109/10253890.2012.686075.
Powe D.G., Voss M.J., Zanker K.S., Habashy H.O., Green A.R., Ellis I.O., Entschladen F. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget. 2010; 1(7): 628–638, doi: 10.18632/oncotarget.101009.
Melhem-Bertrandt A., Chavez-Macgregor M., Lei X., Brown E.N., Lee R.T, Meric-Bernstam F., Sood A.K., Conzen S.D., Hortobagyi G.N., Gonzalez-Angulo A.M. Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J. Clin. Oncol. 2011; 29(19): 2645–2652, doi: 10.1200/JCO.2010.33.4441.
Smith C.J., Minas T.Z., Ambs S. Analysis of Tumor Biology to Advance Cancer Health Disparity Research. Am. J. Pathol. 2018; 188(2): 304–316, doi: 10.1016/j.ajpath.2017.06.019.
Tilan J., Kitlinska J. Sympathetic neurotransmitters and tumor angiogenesis – link between stress and cancer progression. J. Oncol. 2010; 2010: 539706, doi: 10.1155/2010/539706.
Weisenrieder J.S., Neighbors J.D., Mailman R.B., Hohl R.J. Cancer and dopamine D2 receptor: A pharmacological perspective. The Journal of Pharmacology and Experimental Therapeutics. 2019; 370(1): 111–126, doi: 10.1124/jpet.119.256818.
Engwa G.A., Ayuk E.L., Igbojekwe B.U., Unaegbu M. Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives. Biochem. Res. Int. 2016: 9896575, doi: 10.1155/2016/9896575.
Ghinet A., Moise I.M., Rigo B., Homerin G., Farce A., Dubois J., Bicu E. Studies on phenothiazines: New microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents. Bioorg. Med. Chem. 2016; 24(10): 2307–2317, doi: 10.1016/j.bmc.2016.04.001.
Wu B.J., Lin C.H., Tseng H.F., Liu W.M., Chen W.C., Huang L.S., Sun H.J., Chiang S.K., Lee S.M. Validation of the Taiwanese Mandarin version of the Personal and Social Performance scale in a sample of 655 stable schizophrenic patients. Schizophr. Res. 2013; 146(13): 34–39, doi: 10.1016/j.schres.2013.01.036.
Gryz M., Lehner M., Wisłowska-Stanek A., Płaźnik A. Funkcjonowanie układu dopaminergicznego w warunkach stresu – poszukiwanie podstaw różnic indywidualnych, badania przedkliniczne. Psychiatr. Pol. 2018; 52(3): 459–470.
Lehner M.H., Taracha E., Kaniuga E., Wisłowska-Stanek A., Wróbel J., Sobolewska A., Turzyńska D., Skórzewska A., Płaźnik A. Highanxiety rats are less sensitive to the rewarding effects of amphetamine on 50kHz USV. Behav. Brain Res. 2014; 275: 234–242, doi: 10.1016/j.bbr.2014.09.011.
Hill M.N., Hellemans K.G.C., Verma P., Gorzalka B.B., Weinberg J. Neurobiology of chronic mild stress: Parallels to major depression. Neurosci. Biobehav. Rev. 2012; 36(9): 2085–2117, doi: 10.1016/j.neubiorev.2012.07.001.
Marchewka Z., Gielniak M., Piwowar A. Rola wybranych mediatorów procesu zapalnego w patogenezie chorób nowotworowych. Postepy Hig. Med. Dosw. (online) 2018; 72: 175–183.
Paulsen O., Laird B., Aass N., Lea T., Fayers P., Kaasa S., Klepstad P. The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer. PLoS One 2017; 12(5): e0177620, doi: 10.1371/journal.pone.0177620.
Todorović-Raković N., Milovanović J. Interleukin-8 in breast cancer progression. J. Interferon Cytokine Res. 2013; 33(10): 563–570, doi: 10.1089/jir.2013.0023.
Brat D.J., Bellail A.C., Van Meir E.G. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol. 2005; 7(2): 122–133, doi: 10.1215/S1152851704001061.
Irwin M. Immune correlates of depression. Adv. Exper. Med. Biol. 1999; 461: 1–24, doi: 10.1007/978-0-585-37970-8_1.
Liu B., Li Z., Mahesh S.P., Pantanelli S., Hwang F.S., Siu W.O., Nussenblatt R.B. Glucocorticoid-induced tumor necrosis factor receptor negatively regulates activation of human primary natural killer (NK) cells by blocking proliferative signals and increasing NK cell apoptosis. J. Biol. Chem. 2008; 283(13): 8202–8210, doi: 10.1074/jbc.M708944200.
Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell 2000; 100(1): 57–70, doi: 10.1016/s0092-8674(00)81683-9.
Hassan S., Karpova Y., Baiz D., Yancey D., Pullikuth A., Flores A., Register T., Cline J.M., D'Agostino R Jr., Danial N., Datta S.R., Kulik G. Behavioral stress accelerates prostate cancer development in mice. J. Clin. Invest. 2013; 123(2): 874–886, doi: 10.1172/JCI63324.
Nagaraja A.S., Armaiz-Pena G.N., Lutgendorf S.K., Sood A.K. Why stress is BAD for cancer patients. J. Clin. Invest. 2013; 123(2): 558–560, doi: 10.1172/JCI67887.
Sastry K.S., Karpova Y., Prokopovich S., Smith A.J., Essau B., Gersappe A., Carson J.P., Weber M.J., Register T.C., Chen Y.Q., Penn R.B., Kulik G. Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation. J. Biol. Chem. 2007; 282(19): 14094–14100, doi: 10.1074/jbc.M611370200.
Thaker P.H., Han L.Y., Kamat A.A., Arevalo J.M., Takahashi R., Lu C., Jennings N.B., Armaiz-Pena G., Bankson J.A., Ravoori M., Merritt W.M., Lin Y.G., Mangala L.S., Kim T.J., Coleman R.L., Landen C.N., Li Y., Felix E., Sanguino A.M., Newman R.A., Lloyd M., Gershenson D.M., Kundra V., Lopez-Berestein G., Lutgendorf S.K., Cole S.W., Sood A.K. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat. Med. 2006; 12(8): 939–944, doi: 10.1038/nm1447.
Shan T., Ma J., Ma Q., Guo K., Guo J., Li X., Li W., Liu J., Huang C., Wang F., Wu E. β2-AR-HIF-1α: a novel regulatory axis for stress-induced pancreatic tumor growth and angiogenesis. Curr. Mol. Med. 2013; 13(6): 1023–1034, doi: 10.2174/15665240113139990055.
Campbell J.P., Karolak M.R., Ma Y., Perrien D.S., Masood-Campbell S.K., Penner N.L., Munoz S.A., Zijlstra A., Yang X., Sterling J.A., Elefteriou F. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. PLoS Biol. 2012; 10(7): e1001363, doi: 10.1371/journal.pbio.1001363.
Sloan E.K., Priceman S.J., Cox B.F., Yu S., Pimentel M.A., Tangkanangnukul V., Arevalo J.M., Morizono K., Karanikolas B.D., Wu L., Sood A.K., Cole S.W. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010; 70(18): 7042–7052, doi: 10.1158/0008-5472.CAN-10-0522.
Ji H., Liu N., Li J., Chen D., Luo D., Sun Q., Yin Y., Liu Y., Bu B., Chen X., Li J. Oxytocin involves in chronic stress-evoked melanoma metastasis via β-arrestin 2-mediated ERK signaling pathway. Carcinogenesis 2019; 40(11): 1395–1404, doi: 10.1093/carcin/bgz064.
Ścibior-Bentkowska D., Czeczot H. Cancer cells and oxidative stress. Postepy Hig. Med. Dosw. (online) 2009; 63: 58–72.
Behrend L., Henderson G., Zwacka R.M. Reactive oxygen species in oncogenic transformation. Biochem. Soc. Trans. 2003; 31 (Pt 6): 1441–1444, doi: 10.1042/bst0311441.
Zaremba T., Oliński R. Oksydacyjne uszkodzenia DNA – ich analiza oraz znaczenie kliniczne. Postępy Biochemii 2010; 56(2): 124–138.
Sawicka E., Lisowska A., Kowal P., Długosz A. Rola stresu oksydacyjnego w raku pęcherza moczowego. Postepy Hig. Med. Dosw. (online) 2015; 69: 744–752, doi: 10.5604/17322693.1160361.
Malins D.C., Gunselman S.J. Fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry reveal a remarkable degree of structural damage in the DNA of wild fish exposed to toxic chemicals. Proc. Natl. Acad. Sci. USA 1994; 91(26): 13038–13041, doi: 10.1073/pnas.91.26.13038.
Shammas M.A. Telomeres, lifestyle, cancer, and aging. Curr. Opin. Clin. Nutr. Metab. Care 2011; 14(1): 28–34. doi: 10.1097/MCO.0b013e32834121b1.
Blackburn E., Epel E. Telomeres and Adversity: Too Toxic to Ignore. Nature 2012; 490(7419): 169–171, doi: 10.1038/490169a.
Hanssen L.M., Schutte N.S., Malouff J.M., Epel E.S. The Relationship Between Childhood Psychosocial Stressor Level and Telomere Length: A Meta-Analysis. Health Psychol. Res. 2017; 16; 5(1): 6378, doi: 10.4081/hpr.2017.6378.
Robles T.F., Carroll J.E., Bai S., Reynolds B.M., Esquivel S., Repetti R.L. Emotions and family interactions in childhood: Associations with leukocyte telomere length emotions, family interactions, and telomere length. Psychoneuroendocrinology 2016; 63: 343–350, doi: 10.1016/j.psyneuen.2015.10.018.
Jacobs T.L., Epel E.S., Lin J., Blackburn E.H., Wolkowitz O.M., Bridwell D.A., Zanesco A.P., Aichele S.R., Sahdra B.K., MacLean K.A., King B.G., Shaver P.R., Rosenberg E.L., Ferrer E., Wallace B.A., Saron C.D. Intensive meditatin training, immune cell telomerase activity, and psychological mediators. Psychoneuroendocrinology 2011; 36(5): 664–681, doi: 10.1016/j.psyneuen.2010.09.010.
Ornish D., Lin J., Daubenmier J., Weidner G., Epel E., Kemp C., Magbanua M.J.M., Marlin R., Yglecias L., Carroll P.R., Blackburn E. H. Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncology 2008; 9(11): 1048–1057, doi: 10.1016/S1470-2045(08)70234-1.
Maciejowski J., de Lange T. Telomeres in cancer: tumour suppression and genome instability. Nat. Rev. Mol. Cell Biol. 2017; 18(3): 175–186, doi: 10.1038/nrm.2016.171.
Nomikos N.N., Nikolaidis P.T., Sousa C.V., Papalois A.E., Rosemann T., Knechtle B. Exercise, Telomeres, and Cancer: “The Exercise-Telomere Hypothesis”. Front Physiol 2018; 9: 1798, doi: 10.3389/fphys.2018.01798.
Simoes H.G., Sousa C.V., Dos Santos Rosa T., da Silva Aguiar S., Deus L.A., Rosa ECCC., Amato A.A., Andrade R.V. Longer Telomere Length in Elite Master Sprinters: Relationship to Performance and Body Composition. Int. J. Sports Med. 2017; 38(14): 1111–1116, doi: 10.1055/s-0043-120345.
Jośko-Ochojska J. Dziedziczenie traumy. Epigenetyczny „list” do przyszłych pokoleń. W: Medyczne i społeczne aspekty traumy [Jośko-Ochojska J. Inheritance of trauma. Epigenetic “letter” to future generations. In: Medical and social aspects of trauma]. Red. J. Jośko-Ochojska. Śląski Uniwersytet Medyczny. Katowice 2016.
Egger G., Liang G., Aparicio A., Jones P.A. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429(6990): 457–463, doi: 10.1038/nature02625.
Yamaguchi K., Matsumura N., Mandai M., Baba T., Konishi I., Murphy S.K. Epigenetic and genetic dispositions of ovarian carcinomas. Oncoscience 2014; 1(9): 574–579, doi: 10.18632/oncoscience.82.
Wu S.P., Cooper B.T., Bu F., Bowman C.J., Killian J.K., Serrano J., Wang S., Jackson T.M., Gorovets D., Shukla N., Meyers P.A., Pisapia D.J., Gorlick R., Ladanyi M., Thomas K., Snuderl M., Karajannis M.A. DNA Methylation-Based Classifier for Accurate Molecular Diagnosis of Bone Sarcomas. JCO Precis Oncol. 2017; doi: 10.1200/PO.17.00031.
Hauser B.M., Lau A., Gupta S., Bi W.L., Dunn I.F. The Epigenomics of Pituitary Adenoma. Front Endocrinol. (Lausanne) 2019; 14(10): 290, doi: 10.3389/fendo.2019.00290.
Baylin S.B., Jones P.A. A decade of exploring the cancer epigenome –biological and translational implications. Nat. Rev. Cancer 2011; 23; 11(10): 726–734, doi: 10.1038/nrc3130.
Jenuwein T., Allis C.D. Translating the histone code. Science 2001; 293(5532): 1074–1080, doi: 10.1126/science.1063127.
Andersen G.B., Tost J. Circulating miRNAs as Biomarker in Cancer. Recent Results Cancer Res. 2020; 215: 277–298, doi: 10.1007/978-3-030-26439-0_15.
Curia M.C., Fantini F., Lattanzio R., Tavano F., Di Mola F., Piantelli M., Battista P., Di Sebastiano P., Cama A. High methylation levels of PCDH10 predict poor prognosis in patients with pancreatic ductal adenocarcinoma. BMC Cancer 2019; 19(1): 452, doi: 10.1186/s12885-019-5616-2.
Orozco J.I.J., Manughian-Peter A.O., Salomon M.P., Marzese D.M. Epigenetic Classifiers for Precision Diagnosis of Brain Tumors. Epigenet Insights. 2019; 12: 2516865719840284, doi: 10.1177/2516865719840284.
Stepulak A., Stryjecka-Zimmer M., Kupisz K., Polberg K. Inhibitory deacetylaz histonów jako potencjalne cytostatyki nowej generacji. Postepy Hig. Med. Dosw. 2005; 59: 68–74.
Vigushin D.M., Coombes R.C. Histone deacetylase inhibitors in cancer treatment. Anticancer Drugs 2002; 13(1): 1–13, doi: 10.1097/00001813-200201000-00001.
Kim H.J., Bae S.C. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am. J. Transl. Res. 2011; 3(2): 166–179.
Grabarska A., Dmoszyńska-Graniczka M., Nowosadzka E., Stepulak A. Inhibitory deacetylaz histonów – mechanizmy działania na poziomie molekularnym i zastosowania kliniczne. Postepy Hig. Med. Dosw. 2013; 67: 722–735.
Li L.C., Carroll P.R., Dahiya R. Epigenetic changes in prostate cancer: implication for diagnosis and treatment. J. Natl. Cancer Inst. 2005; 97(2): 103–115, doi: 10.1093/jnci/dji010.
Ho E., Beaver L.M., Williams D.E., Dashwood R.H. Dietary Factors and Epigenetic Regulation for Prostate Cancer Prevention. Adv. Nutr. 2011; 2(6): 497–510, doi: 10.3945/an.111.001032.
Shukla S., Penta D., Mondal P., Meeran S.M. Epigenetics of Breast Cancer: Clinical Status of Epi-drugs and Phytochemicals. Adv. Exp. Med. Biol. 2019; 1152: 293–310, doi: 10.1007/978-3-030-20301-6_16.
Kruk J., Aboul-Enein B.H, Bernstein J., Gronostaj M. Psychological Stress and Cellular Aging in Cancer: A Meta-Analysis. Oxid. Med. Cell. Longev. 2019; 2019: 1270397, doi: 10.1155/2019/1270397.
Schraub S., Sancho-Garnier H., Velten M. Should psychological events be considered cancer risk factors? Rev. Epidemiol. Sante Publique 2009; 57(2): 113–123, doi: 10.1016/j.respe.2008.12.012.
Denaro N., Tomasello L., Russi E.G. Cancer and stress: what’s matter? From epidemiology: the psychologist and oncologist point of view. Journal of Cancer Therapy & Research 2014; 3(6): 1–11, doi: 10.7243/2049-7962-3-6.