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ABSTRACT
Original Scientific Article
Mac Vet Rev 2016; 39 (2): i-viii
Available online at
www.macvetrev.mk
Macedonian Veterinary Review
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.
Key words: dog, stress, tumor, problem behavior
INTRODUCTION
A considerable amount of studies demonstrate
that negative psychological states, such as chronic
stress, depression, social isolation, are associated
with the down-regulation of the cellular immune
response mediated by adrenergic and glucocorticoid
STRESS AND CANCER IN DOGS: COMPARISON BETWEEN
A POPULATION OF DOGS DIAGNOSED WITH CANCER AND
A CONTROL POPULATION - A PILOT STUDY
Simona Cannas1, Greta Veronica Berteselli2, Patrizia Piotti3, Zita Talamonti1,
Elisabetta Scaglia1, Damiano Stefanello1, Michela Minero1, Clara Palestrini1
1Dipartimento Medicina Veterinaria (DIMEVET),
Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy
2via Giotto 20, 20060 Masate, Milano, Italy
3Department of Psychology, University of Portsmouth, King Henry Building,
King Henry 1st Street, Portsmouth, PO1 2DY, UK
Received 8 March 2016; Received in revised form 17 May 2016; Accepted 31 May 2016
Corresponding author: Dr. Simona Cannas, PhD
E-mail address: simona_cannas@hotmail.com
Present address: Dipartimento di Medicina Veterinaria (DIMEVET),
Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy
Phone: 0039 3803185036; Fax: 0039 0250318030
Copyright: © 2016 Cannas S. This is an open-access article published
under the terms of the Creative Commons Attribution License which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Competing Interests: The authors have declared that no competing
interests exist.
Available Online First: 16 June 2016
http://dx.doi.org/10.1515/macvetrev-2016-0088
signaling, which increases the risk of developing
diseases (1-7). Although there is no unanimity in the
literature, results from both human and laboratory
animal studies suggest that psychological factors
and chronic stress may promote the onset and the
progression of cancer (6, 8, 9, 10, 11).
Stress is the general reaction of the organism
when the homeostasis is altered by physical and
psychological factors called “stressors” (12, 13).
When in this state, the body activates physiological
and immunological mechanisms: these modulate
physical and behavioral functions aimed at adapting
to the new situation and restore the initial homeostasis
(4, 13, 14, 15). Stress and the immune system are
therefore closely related. In fact, the stress response
is thought to have evolved phylogenetically from a
primitive humoral immune system, aimed to face
internal or external challenges to the organism (16).
ii
The exchange of information, directly or
through the neuroendocrine system, between
brain and immune system creates a “psycho-
neural-endocrine-immune circuit” (17, 18). The
consequence is that when the homeostasis cannot
be restored, the prolonged effect of stressors may
induce an immune dysregulation modulated by the
endocrine system. Particularly, stress can inhibit
the immune-surveillance activity of T cells and
Natural Killer cells (NK), which intervene in the
immune-surveillance against tumors (19, 20). Stress
hormones such as cortisol, catecholamine and other
endocrine mediators can promote proliferation of
neoplastic cells, and inhibit the mechanisms that
eliminate altered cells, such as apoptosis and DNA
repair systems. Cortisol and catecholamine can
also facilitate tumor development mechanisms,
such as angiogenesis and metastasis (6, 21, 22, 23).
Therefore, while the stress response is not thought
to cause tumors directly, it appears that chronic
stress can promote the incidence and progression
of cancer, with similar mechanisms in humans and
animals such as the domestic dog. This relies on
the relationships between stress system, immune
system and carcinogenic mechanisms (21, 24).
A large amount of evidence also demonstrated
that anxiety, phobia, fear, depression and chronic
stress induces changes in the neuroendocrine system
in human beings (1-7, 32), and that such changes
also occur in pet dogs showing behavioral problems
(15, 25, 26, 27, 30, 31).
Several problem behaviors are recognized as
biological indicators of poor welfare in dogs because
they can be symptoms of chronic stress (15, 28, 40).
However, it should be considered that though the
stress system acts in the same way in all individuals,
coping to stress depends on several factors as
individual and genetic differences, developing
phases, life experiences and household (15, 27, 41).
There is evidence to support the use of domestic
dogs as models for the study of the relation between
stress and cancer from a comparative point of
view (34, 35). As for humans, stress can become
detrimental for dogs’ wellbeing when it becomes
chronic or the animal is unable to cope and restore
homeostasis (15, 25, 26). Anxiety-related disorders
are among the most common behavioral problems
in pet dogs, and their behavioral manifestations are
indeed considered good indicators for monitoring
the presence of stress (15, 25, 26, 27, 28).
Additionally, the stress system is controlled by the
same physiological mechanisms in dogs and humans
(4, 12, 29, 30), and most of dogs’ behavioral
problems have neuropathological bases similar to
that of certain psychological disorders in humans
such as depression, anxiety and phobias (27, 31). For
example, dogs affected by anxiety related disorders
have high cortisol blood levels similar to humans
(28, 32). Finally, several types of the spontaneous
tumors occurring in pet dogs share numerous
features with those of humans, such as genetic
characteristics, histopathological appearance,
biological behavior, molecular targets and response
to conventional cancer therapy (33, 34, 35).
The current retrospective cohort pilot study aims
to analyze the relation between stress and cancer in
pet dogs by evaluating and comparing the stress
level in two groups: one group consisting of dogs
diagnosed with malignant tumors, the other group
consisting of healthy control dogs (i.e. without
oncological diagnoses or other medical diagnoses).
MATERIAL AND METHODS
Subjects
Two groups of 69 dogs each, balanced for sex
and age, were included in the study. The first group
(hereafter named “oncologic group”) consisted of
dogs with a previous diagnosis of a spontaneous
malignant tumor. Dogs in this group were recruited
through the Department of Veterinary Science and
Public Health at the Veterinary University from
June 2006 to May 2009. The inclusion criterion was
a cytological or histological definitive diagnosis of
malignant neoplasia. The second group (“control
group”) consisted of healthy dogs with no signs
of clinical diseases, and not previously affected by
tumors. Subjects in the control group were recruited
from personal contacts trough the Hospital, during
the same time frame. Oncologic and control dogs
underwent a physical examination, and had a
complete blood count and biochemistry panel
performed.
Data collection
Dogs’ owners were asked to complete a
questionnaire including their dog’s demographic
information and behavioral history, as well as
information on the dog’s physical and social
environment. For the oncologic group, owners were
explicitly required to provide information about the
dog’s behavior and lifestyle before the diagnosis of
neoplasia.
Through open questions, owners provided
information about the signalement, medical and
behavioral history of their dog. The other sections
of the questionnaire were composed of multiple
choice questions: a first part provided information
about home environment, animal management, age
of the animal (current age, and age at acquisition),
sex, reproductive status (intact or neutered/spayed),
Cannas S. et al.
iii
number of adults and children in the household
(people older than 18 years were considered adults),
origin of the dog (breeder, pet store, shelter, rescue,
family, friends or stray), and number of other pets in
the household. A second part provided information
about whether the dog had displayed specific
signs compatible with behavioral problems, such
as fear, anxiety, separation anxiety, aggression or
compulsive disorders.
Statistical analysis
Answers to the questionnaire were scored
and the data were entered into Microsoft Excel
(Microsoft Corporation 2010) and analyzed with
SPPS statistical package (IBM SPSS Statistic
21). Descriptive statistics (relative proportions,
minimum and maximum values, median, mean and
standard deviations) were calculated to provide a
general description of the two experimental groups.
Any differences in behavior, management
and environment between the oncologic and the
control group, were verified using a ChiSquare
test. Differences were considered to be statistically
significant if p ≤ 0.05. A Decision Tree model was
performed as descriptive means to identify the
variables, and their probability of predicting the
development of tumors in pet dogs.
RESULTS
Dogs were 12 intact and 37 spayed females, 5
neutered and 15 intact males ranging in age from
2 and 16 years (mean 8,29 ± 2,6 years) for both
groups.
In the oncologic group 62% of dogs were pure
breeds; the remaining 38% were mixed breeds. In the
control group, 56% of dogs were pure breeds, while
44% were mixed breeds. Breeds were divided into
groups according to the Official Dog Breeds List
of the Italian Kennel Club: Sheepdogs and Cattle
dogs [1], Pinschers, Schnauzers and Molossers [2],
Terriers [3], Dachshunds [4], Spitz and primitive
type dogs [5], Hounds and blood tracking dogs [6],
Pointing dogs [7], Retrievers, search dogs, water
dogs [8], Companion dogs [9], Greyhounds [10].
More information about breeds is specified in
Table 1. The oncologic diagnoses are summarized
in Fig. 1.
Group
1Group
2Group
3Group
4Group
5Group
6Group
7Group
8Group
9Group
10 Mixed
breed
Oncologic
group 10% 30% 3% 0 1% 0 9% 9% 0 0 38%
Control
group 10% 6% 10% 0 4,5% 3% 0 18% 4,5% 0 44%
Table 1. Percentage of dog breeds in the two groups
Twenty-five per cent of the dogs in both groups
were adopted before 7 weeks of age, about 35%
between eight and 13 weeks, 7% between 6 months
and one year and about 15% after 1 year of age. The
remaining 53% were either younger than 7 weeks or
older than 1 year, when adopted.
In the oncologic group, most dogs (39%) were
adopted from private non-breeders, followed by
23% adopted directly from breeders. The remaining
dogs were adopted from a pet store (1%), from local
shelter (15%) or were strays (15%). In the control
group, 12% of dogs were adopted from non-breeders
and 36% from breeders. The remaining control
dogs had similar origins as the oncologic dogs with
7% from pet stores; about 15% from shelters and
another 15% were strays.
At the time of adoption, about half of dogs
from both groups were with the mother and other
littermates; 29% of oncologic dogs and 17% of
control dogs were alone when adopted (which
includes dogs adopted as puppies and adults). In
both groups, about 60% lived their lives with three
or more people in the household and about 13%
lived with only one owner.
Fifty-four percent of oncologic dogs and 27%
control dogs were the only pet in the household.
Of the remaining oncologic dogs, 25% lived with
other dogs, 12% lived with cats, 10% lived with
another dog and cat, and 4% lived with other animal
Figure 1. Oncologic diagnosis
Stress and cancer in dogs
iv
species. The distribution of remaining control dogs
was similar to the oncologic group. No cohabitation
problems were reported in 90% of both groups. In
the oncologic group, 78% of the dogs experienced
changes in the household: 23% were permanently
separated from a family member, e.g. because of
death, 12% arrival of a new family member, e.g.
newborns or marriages, 4% moving house, 4%
substantial changes in the daily routine, e.g. changes
in owners’ working shifts, 35% more than one
change. 58,1% of dogs belonging to the oncologic
group and 41,9% of dogs belonging to the control
one had changes in the household (p<0.05) (Fig. 2).
Figure 2. Percentage of dogs that had changes in the
household (p<0.05)
Attention seeking behavior and following
the owners everywhere around the house were
significantly higher in the oncologic group
(attention seeking 62%; following 68%) with
respect to the controls (attention seeking 38%;
following 32%) (p<0.05). The percentage of dogs
hiding without a specific reason was 75,6% in
the oncologic group and 24,4% in the control one
(p<0.05). Furthermore, oncologic dogs proved to be
significantly more vigilant (58,8%) and fearful of
fireworks and gunshots (62%) than controls (hyper-
vigilance 41,2%; fear of fireworks and gunshots
38%) (p<0.05).
67 % of oncologic dogs and 33% of controls
showed aggressive behaviors towards people
(p<0.05). Similarly, 68% of dogs of the oncologic
group as opposed to 32% belonging to the control
one showed aggression towards other dogs (p<0.05).
The percentage of dogs that lick and chew
excessively parts of their body was significantly
higher in the oncologic group (74%) than in the
control group (26%) (p<0.05). These results are
summarized in Fig. 5.
Figure 3. Percentage of dogs that had a lack of routine
(p<0.05)
Figure 4. Percentage of dogs that had surgery or
traumatic event (p<0.05)
Cannas S. et al.
Lack of daily routine, for feeding time, walks
and/or interaction with owners, was significantly
higher in the oncologic group (84.4%) than in the
control group (15,6%) (p<0.05) (Fig. 3).
The percentage of surgery or a traumatic event
before the diagnosis of neoplasia was 63,5% in the
oncologic group and 36,5% in the control group
(p<0.05) (Fig. 4).
Figure 5. Percentage of dogs showing different
stress-related behaviors
v
Stress and cancer in dogs
The Decision Trees identified the lack of routine
as the factor that mainly predicts the dependent
variable considered (tumor prevalence) (p=0.000;
CHI-Square=31.689; df=1).
DISCUSSION
The two groups of dogs in our study are
homogenous regarding sex, age and source of the
subjects. This is relevant because these variables
can play an important role in veterinary oncology,
where in subjects older than 7 years and in certain
breeds the incidence of malignant neoplasia is more
prevalent (36).
We found that significantly more dogs of the
oncologic group, as opposed to the control group,
experienced substantial changes in the household.
Environmental or social factors unpredictability
intervenes in the development of behavioral
disorders. When an individual is unable to adapt to
a new or unpredictable environment, stress becomes
chronic, thus leading to physical and behavioral
consequences (4, 30, 37, 38). This is supported by
evidence in the human literature, where the loss of
a family member or changes in living conditions
are particularly stressful situations which are also
associated to an increased prevalence of tumors
(2, 3, 4).
From the results of this study, it is possible to
conclude that more dogs in the oncologic group have
been exposed to major stress events as opposed to the
control group. Pet animals are often confronted with
unpredictable and uncontrollable life events, such
as changes in the social core group (e.g. children
leaving the house, babies being born, divorce, etc.),
changes in the physical environment (e.g. moving
to another place), or both. Unpredictable major life
events can lead to gross behavioral dysfunctions,
such as increased stress and (pathological) anxiety
(39).
A higher number of dogs in the oncologic group
underwent a surgery or experienced a traumatic
event than in the control group. This is interesting
because several aspects of surgery are implicated in
immunosuppression, e.g. anesthetic and analgesic
drugs, hypothermia, tissue damage, blood loss and
transfusion, nociception, pain, and perioperative
anxiety and stress (22). There is also empirical
evidence, from animal and human studies, of the
promotion of metastasis induced by stress and
surgery, with specific reference to the mediating
role of cell-mediated immunity (22).
The oncologic dogs in this study also showed
significantly more behaviors that are signs of stress
and anxiety (40, 41, 42) and that can be related with
behavioral disorders (15, 27, 25, 26).
Finally, the factor that discriminated the two
groups, marking out the oncologic group, was the
lack of routine, which was the better predictor
variable of the Decision Trees.
For dogs, it is essential to have a daily routine
related to time of feeding, walking and interaction
because this leads to a predictable environment.
Situations characterized by lack of routine or
unpredictability changes of social and physical
environment can be stressors and a triggering event
to onset behavioral problems, especially in those
subjects that are not able to show correct behaviors
to cope in stress situation (15, 26, 39, 43, 44).
The resulting chronic stress could interfere with
neuroendocrine and immune processes altering the
organism’s defenses, increasing the risk for several
conditions, including cardiovascular disease, type
2 diabetes, mental health complications, and some
cancers (45, 46).
The effects of behavioral stress on tumor
initiation and progression are complex and
should be analyzed in the context of relevant
microenvironment biology (6, 21).
Our study shows several limitations. Some
breeds may be both more cancer prone and more
prone to stress, but that does not prove causality and
in our study it was not possible to evaluate eventual
breed bias. The major limitations of this work is
that, being retrospective, is very difficult to make
any conclusions regarding the evaluation of specific
previous behaviours in the dogs’ life, but 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 in their
previous life compared to control dogs.
In this study, we focused on the interaction
between bio-behavioral factors and cancer in pet
dogs. In light of the results of our study, it is clear
that spontaneous tumors in companion animals offer
a unique opportunity to investigate the relationship
between stress and cancer and that dogs are good
models for human cancer biology. The relatively
high incidence of some types of cancer, similarity in
biologic behavior, large body size, and comparable
responses to cytotoxic agents are some of the
similarities in dogs and humans (34, 35). For the
aforementioned reasons, further research should be
established in order to obtain additional information
regarding the link between tumor and stress.
Specifically, we suggest that future studies should
focus on the analysis of the possible application
of behavioral, neuroendocrine and immune stress
markers to this area of research, such as cortisol,
serotonine, dopamine, IgA, lysozyme (28, 47, 48,
49, 50). It would be also beneficial to increase the
vi
sample size in order to focus on a specific type
of neoplasia: for example, canine lymphoma is
considered the most suitable type of canine tumor in
the field of comparative oncology (35).
The comparative study of the effect of stress on
tumors is promising. In addition to the increasing
understanding of the cancerogenesis process, it
offers, in the long term, opportunities for innovative
therapeutic interventions. These could be based
on combined behavioral and pharmacological
approaches, aimed at tumor-supporting immune-
neuroendocrine processes; such approaches may
be integrating, or being used in combination with
conventional therapies (6, 51).
ACKNOWLEDGEMENT
The authors thank all the owners and dogs that
participated as volunteers.
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Cannas S. et al.
Please cite this article in press as: Cannas S., Berteselli G.V., Piotti P., Talamonti Z., Scaglia E., Stefanello D., Minero M.,
Palestrini C. Stress and cancer in dogs: Comparison between a population of dogs diagnosed with cancer and a control population- A
pilot study. Mac Vet Rev 39(2): i-viii. http://dx.doi.org/10.1515/macvetrev-2016-0088