ORIGINAL_ARTICLE Stress and cancer in dogs: Comparison between a population of dogs diagnosed with vancer and a control population - A pilot study It is widely accepted that psychological stress and mental illness can compromise the function of the immune system. Clinical and epidemiological studies on humans recognized that specific psychosocial factors, such as stress, chronic depression and lack of social support are risk factors for the development and progression of cancer. Unfortunately, most of the animals studies on this subject are based on laboratory tests performed on mice. This retrospective cohort study aims to analyze the relation between stress and tumor in pet dogs, by evaluating and comparing the stress level in two groups of 69 dogs each, balanced for sex and age: the oncologic group consists of dogs diagnosed with cancer and the control group consists of healthy dogs. Our results show that, before the cancer diagnosis, more dogs in the oncologic group faced changes in their household and routine as opposed to the control group (p<0.05). More dogs of the oncologic group than the control group also showed signs of stress and anxiety, before the cancer diagnosis (p<0.05). As reported by their owners, these included attention seeking, hiding without a specific reason, following the owner around the house, hyper-vigilance, fear of fireworks and gunshots, biting, aggression towards other dogs, licking and chewing excessively parts of their body. Our results are aligned with the evidence from human research, indicating that dogs with cancer are significantly more likely to have shown signs of stress compared to the control dogs during their life. https://macvetrev.mk/Files/Article/2019/10.1515/macvetrev-2016-0088/macvetrev-2016-0088.pdf 2016-10-15T09:00:00 201 208 10.2478/macvetrev-2016-0088 dog stress tumor problem behavior Simona Cannas simona_cannas@hotmail.com false 1 Dipartimento Medicina Veterinaria (DIMEVET),Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy LEAD_AUTHOR Greta Veronica Berteselli false 2 via Giotto 20, 20060 Masate, Milano, Italy AUTHOR Patrizia Piotti false 3 Department of Psychology, University of Portsmouth, King Henry Building, King Henry 1st Street, Portsmouth, PO1 2DY, UK AUTHOR Zita Talamonti false 4 Dipartimento Medicina Veterinaria (DIMEVET),Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy AUTHOR Elisabetta Scaglia false 5 Dipartimento Medicina Veterinaria (DIMEVET),Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy AUTHOR Damiano Stefanello false 6 Dipartimento Medicina Veterinaria (DIMEVET),Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy AUTHOR Michela Minero false 7 Dipartimento Medicina Veterinaria (DIMEVET),Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy AUTHOR Clara Palestrini false 8 Dipartimento Medicina Veterinaria (DIMEVET),Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy AUTHOR Leonard B.E, Song C, Stress and the Immune System in the Etiology of Anxiety and DepressionPharmacol. Biochem. Behav 1996; 54: 1299-303. 1 10.1016/0091-3057(95)02158-2 Graham J, Ramirez A, Love S, Richards M, Burgess C, Stressful life experiences and risk of relapse of breast cancer: observational cohort studyBrit. Med. J 2002; 324: 73511420-1424. PMid: 12065263 PMCid: PMC115851 2 10.1136/bmj.324.7351.1420 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 studyAm. J. Epidemiol 2003; 157: 5415-423. PMid: 12615606 3 10.1093/aje/kwg002 Kyrou I, Tsigos C, Stress mechanisms and metabolic complicationsHorm. Metab. Res 2007; 39: 6430-438. PMid 17578760 4 10.1055/s-2007-981462 Kruk J, Aboul-Enein H.Y, Psychological stress and the risk of breast cancer: a case-control studyCancer Detect. Prev 2004; 28: 6399-408. PMid: 15582263 5 10.1016/j.cdp.2004.07.009 Armaiz-Pena G.N, Lutgendorf S.K, Cole S.W, Sood A.K, Neuroendocrine modulation of cancer progressionBrain Behav. Immun 2009; 23: 110-15. PMid: 18638541 PMCid: PMC2630522 6 10.1016/j.bbi.2008.06.007 Lutgendorf S.K, Sood A. K, Biobehavioral factors and cancer progression: physiological pathways and mechanismsPsychosom. Med 2011; 73: 9724-730. PMid: 22021459 PMCid: PMC3319047 7 10.1097/PSY.0b013e318235b.e76 Rabin B.S, Stress, immune function and health: the connection 1999; New York, NY: Wiley-Liss Sons Inc; 8 Yang E.V, Glaser R, Stress-induced immunomodulation: implication for tumorigenesisBrain Behav. Immun 2003; 17: 37-40. 9 10.1016/S0889-1591(02)00064-8 Reiche E.M, Nunes S.O, Morimoto H.K, Stress, depression, the immune system, and cancerLancet Oncol 2004; 5: 617-625. 10 10.1016/S1470-2045(04)01597-9 Azpiroz A, De Miguel Z, Fano E, Vegas O, Relations between different coping strategies for social stress, tumor development and neuroendocrine and immune activity in male miceBrain, Behav. Immun 2008; 22: 690-698. PMid: 18061400 11 10.1016/j.bbi.2007.10.007 Selye H, A syndrome produced by diverse nocious agentesNature 1936; 138: 32- 12 10.1038/138032a0 Neylan T.C, Hans Selye and the field of stress researchNeuropsychiatry Classics 1998; 10: 2230-231. 13 10.1176/jnp.10.2.230 Breazile J.E, Physiologic basis and consequences of distress in animalsJ. A. V. M. A 1987; 191: 101212-1215. 14 Casey R, Horwitz D, Mills D, Heath S, Fear and stress in companion animalsBSAVA Manual of Canine and Feline Behavioural Medicine 2002; Gloucester, UK: British Small Animal Veterinary Association; 144-153.PMid: 12124759 15 Le Roith D, Shiloach J, Roth J, Is there an earlier phylogenetic precursor that is common to both the nervous and endocrine systems?Peptides 1982; 3: 211-215. 16 10.1016/0196-9781(82)90080-8 Black H.P, Immune system-central nervous system interaction: effect and immunomodulatory consequences of immune system mediators on the brainAntimicrob. Agents Ch 1994; 38: 17-12. 17 10.1128/AAC.38.1.7 Dantzer R, Kelley K.W, Stress and immunity: an integrated view of relationships between the brain and the immune systemLife Sci 1989; 44: 261995-2008. 18 10.1016/0024-3205(89)90345-7 Dunn G.P, Old L.J, Schreiber R.D, The immunobiology of cancer immunosurveilance and immunoeditingImmunity 2004; 21: 137-148. PMid: 15308095 19 10.1016/j.immuni.2004.07.017 Lang K, Entschladen F, Weidt C, Zaenker K, Tumor immune escape mechanisms: impact of the neuroendocrine systemCancer Immunol. Immun 2006; 55: 7749-776. PMid: 16435128 20 10.1007/s00262-006-0126-x Antoni M.H, Lutgendorf S.K, Cole S.W, Dhabhar F.S, Sephton S.E, Green McDonalc P, Stefanek M, Sood Anil K, The influence of bio-behavioural factors on tumours biology: pathways and mechanismsNat. Rev. Cancer 2006; 6: 3240-248. PMid: 16498446 PMCid: PMC3146042 21 10.1038/nrc1820 Ben-Eliyahu S, The promotion of tumor metastasis by surgery and stress: Immunological basis and implication for psychoneuroimmunologyBrain Behav. Immun 2003; 17: 27-37. 22 10.1016/S0889-1591(02)00063-6 Thaker P.H, Sood A.K, Neuroendocrine influences on cancer biologySemin. Cancer Biol 2008; 164-170. 23 10.1016/j.semcancer.2007.12.005 Kiecolt-Glaser J.K, Preacher K.J, MacCallum R.C, Atkinson C, Malarkey W.B, Glaser R, Chronic stress and age-related increases in the proinflammatory cytokine IL-6Proceedings of the National Academy of Sciences 2003; 100: 9090-9095.US. PMid: 12840146 PMCid: PMC166443 24 10.1073/pnas.1531903100 Mills D.S, Dube M.B, Zulch H, Stress and pheromonatherapy in small animal clinical behaviour 2012; Oxford: Wiley-Blackwell; 25 10.1002/9781118702642 Mills D, Karagiannis C, Zulch H, Stress-Its effects on health and behavior: A guide for practitionersVet. Clin. N. Am. Small 2014; 44: 3525-541. PMid: 24766698 26 10.1016/j.cvsm.2014.01.005 Overall K.L, Clinical behavioral medicine for small animals 1997; St. Louis: Mosby-Year Book Inc; 209-250. 27 Berteselli G, Servida F, Dall’Ara P, Verga M, Piola E, Puricelli M, Palestrini C, Mills D, Levine E, Landsberg G, Horwitz A.E, Duxbury A.E, Evaluation of immunological, stress and behavioural parameters in dogs (Canis familiaris) with anxiety-related disordersCurrent Issues and Research in Veterinary Behavioral Medicine 2005; USA: Purdue Press; 18-22. 28 Debenedetti A, Aguggini G, Beghelli V, Giulio L.F, EndocrinologiaFisiologia degli Animali Domestici 1998; Torino: UTET; 645-748. 29 Veissier I, Boissy A, Stress and welfare: two complementary concepts that are intrinsically related to the animal’s point of viewPhysiol. Behav 2007; 92: 3429-433. PMid: 17182067 30 10.1016/j.physbeh.2006.11.008 Overall K.L, Natural animal models of human psychiatric conditions: assessment of mechanism and validityProg. Neuro-Psychoph 2000; 24: 5727-776. 31 10.1016/S0278-5846(00)00104-4 Takahashi T, Ikeda K, Ishikawa M, Kitamura N, Tsukasaki T, Nakama D, Kameda T, Anxiety, reactivity, and social stress-induced cortisol elevation in humansNeuroendocrinol. Lett 2005; 26: 4351-354.PMid: 16136010 32 MacEwen E.G, Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatmentCancer Metast. Rev 1990; 9: 2125-136. PMid: 2253312 33 10.1007/BF00046339 Vail D.M, MacEwen E.G, Spontaneously occurring tumors of companion animals as models for human cancerCancer Invest 2000; 18: 8781-792. PMid: 11107448 34 10.3109/07357900009012210 Borgatti A, Buracco P, Un legame che va oltre l’amicizia: cane, uomo ed oncologia comparataVeterinaria 2009; 23: 29-25. 35 Lagadic M, A.A V.v, I diversi fattori predisponenti le neoplasieOncologia pratica del cane e del gatto. Collana di Summa - animali da compagnia 2006; Milano: Le Point Vétérinaire Italie; 9-13. 36 Glaser R, Kiecolt-Glaser J, Stress-induced immune dysfunction: implications for healthNat. Rev. Immunol 2005; 5: 243-251. PMid: 15738954 37 10.1038/nri1571 Danzer R, Mormede P, Pituitary adrenal consequence of adjunctive behaviours in pigsHorm. Behav 1981; 15: 386-395. 38 10.1016/0018-506X(81)90003-9 Ohl F, Arndt S.S, van der Staay F.J, Pathological anxiety in animalsVet. J 2008; 175: 18-26. PMid: 17321766 39 10.1016/j.tvjl.2006.12.013 Cannas S, Frank D, Minero M, Aspesi A, Benedetti R, Palestrini C, Video analysis of dogs suffering from anxiety when left home alone and treated with clomipramineJournal of Veterinary Behavior: Clinical Applications and Research 2014; 9: 250-57. 40 10.1016/j.jveb.2013.12.002 Godbout M, Beauchamp G, Palestrini C, Frank D, Puppy behavior at the veterinary clinic: a pilot studyJ. Vet. Behav.: Clin. Appl. Res 2007; 2: 126-135. 41 10.1016/j.jveb.2007.06.002 Palestrini C, Minero M, Cannas S, Rossi E, Frank D, Video analysis of dogs with separation-related behaviorsAppl. Anim. Behav. Sci 2010a; 124: 61e67- 42 Flannigan G, Dodman N.H, Risk factors and behaviors associated with separation anxiety in dogJ. A. V. M. A 2001; 219: 4460-466. 43 10.2460/javma.2001.219.460 cGreevy P.D, Masters A.M, Risk factors of separation-related distress and feed-related aggression in dogs: additional findings from a survey in Australian dog ownersAppl. Anim. Behav. Sci 2008; 109: 320-328. 44 10.1016/j.applanim.2007.04.001 Godbout G.P, Glaser R, Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancerJ. Neuroimmune Pharmacol 2006; 1: 4421-427. PMid: 18040814 45 10.1007/s11481-006-9036-0 MacEwen B.S, Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediatorsEur. J. Pharmacol 2008; 583: 2-3174-185. PMid: 18282566 PMCid: PMC2474765 46 10.1016/j.ejphar.2007.11.071 Skandarkumar S, Stodulski G, Hau J, Salivary IgA: a possible stress marker in dogsAnim. Welfare 1995; 4: 4339-350. 47 Beerda B, Schilder M.B.H, van Hooff JARAM, de Vries H.W, Mol J.A, Behavioural and hormonal indicators of enduring environmental stress in dogsAnim. Welfare 2000; 9: 49-62. 48 Yang Y, Koh D, Ng V, Lee C.Y, Dong F, Goh S.H, Anantharaman V, Chia S.E, Self-perceived work related stress and the relation with salivary IgA and Lysozyme among emergency department nursesOccup. Environ. Med 2002; 59: 836-841. PMid: 12468751 PMCid: PMC1763606 49 10.1136/oem.59.12.836 Ng V, Koh D, Mok B.Y.Y, Chia S.E, Lim L.P, Salivary biomarkers associated with academic assessment stress among dental undergraduatesJ. Dent. Edu 2003; 67: 101091-1094.PMid: 14587673 50 Frick L.R, Rapanelli M, Cremaschi G.A, Genaro A.M, Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanismsBrain Behav. Immun 2009; 23: 136-40. PMid: 18625298 51 10.1016/j.bbi.2008.06.010