The Veterinary Journal 186 (2010) 364–369

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The Veterinary Journal

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Association between environmental dust exposure and lung cancer in dogs

Giuliano Bettini a,*, Maria Morini a, Laura Marconato b, Paolo Stefano Marcato a, Eric Zini c
a
Department of Veterinary Public Health and Animal Pathology, Faculty of Veterinary Medicine, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Italy
b
Animal Oncology and Imaging Center, Rothusstrasse 2, Hünenberg, Switzerland
c
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland

a r t i c l e i n f o a b s t r a c t

Article history: The objective of this study was to investigate the relationship between the accumulation of black dust
Accepted 5 September 2009 matter in lungs (anthracosis) and primary lung cancer in dogs. A retrospective study was carried out
on material from 35 dogs with primary lung cancer and 160 controls. The amount, histological appear-
ance and birefringence of anthracosis were assessed in pulmonary specimens by light microscopy, and
Keywords: the odds ratio (OR) calculated for dogs with primary lung cancer. The same factors were analysed to iden-
Lung cancer tify an association between tumour histotype, histological grade, and clinical stage. Papillary adenocar-
Anthracosis
cinoma was most commonly diagnosed (45.7%). The majority of tumours were of histological grade II,
Air pollution
Dog
and the lung cancer was more often localised (clinical stage I). An increased risk of lung cancer was
observed in dogs with higher amounts of anthracosis (OR: 2.11, CI 95%: 1.20–3.70; P < 0.01), which sug-
gests an association between anthracosis due to inhalation of polluted air and lung cancer in dogs.
Ó 2009 Elsevier Ltd. All rights reserved.

Introduction (anthracosis), representing an accurate indicator for lung exposure

Lung cancer is the leading cause of tumour-related mortality
among people in Western industrialised countries, with cigarette
smoking being most frequently responsible (World Health Organi-
zation, 2009). Notably, a subset of affected patients never smoked,
suggesting that exposure to other carcinogens, environmental or
occupational, may promote lung cancer development (Subramani-
an and Govindan, 2007).
Urban air pollutants, notably particulate matter (PM), have been
investigated as potential causal agents for the observed increased
incidence of lung cancer (Nafstad et al., 2003; Vineis and Husgaf-
vel-Pursiainen, 2005; Beelen et al., 2008). PM comprises a complex
mixture of particles that vary not only in size and morphology, but
also in their chemical, physical, and biological characteristics. PM is
usually classified in terms of aerodynamic size as 610 lm (PM10)
or 62.5 lm (PM2.5). PM2.5 particles are dominated by products of
combustion and secondary atmospheric chemistry processes,
while PM10 consist mainly of crustal, biological and mechanically
derived particle fraction components (Mehtaa et al., 2008).
Different aerodynamic sizes of PM have a varying ability to pen-
etrate the respiratory system, with fine particles reaching the dee-
per regions of the lungs, and coarse PM being deposited in the
upper airway (Mehtaa et al., 2008; Valavanidis et al., 2008). Com-
bustion-derived fine particles (PM2.5) accumulate in the lung
parenchyma over time, and their presence is demonstrated by tis-
sue deposition of black dusty material within lung macrophages
* Corresponding author. Tel.: +39 051 2097969; fax: +39 051 2097968.
E-mail address: giuliano.bettini@unibo.it (G. Bettini).
to air pollutants (Balchum et al., 1963). Several chemicals associ-
ated with PM and black matter deposition in the lung parenchyma
have been associated with lung carcinogenesis, particularly poly-
cyclic aromatic hydrocarbons (PAHs) and trace metals, such as ar-
senic, nickel, chromium, and cadmium (Valavanidis et al., 2008).
PAHs are produced during incomplete combustion of a large
variety of hydrocarbons, and are able to damage DNA, induce
mutations and initiate carcinogenesis. Among PAH compounds,
benzo(a)pyrene is recognised as the single most important carcin-
ogen (Wang et al., 2003; Mehtaa et al., 2008). Trace metals,
although poor mutagens and carcinogens per se, can enhance the
mutagenicity and carcinogenicity of other compounds, such as
PAHs (Hu et al., 2004) and facilitate the generation of reactive oxy-
gen species (ROS), which cause a significant increase in oxidative
stress and lipid peroxidation. Furthermore, PAHs, heavy metals
and aldehydes associated to PM have been found to inhibit DNA re-
pair capacity and therefore enhance mutagenesis and carcinogen-
esis (Mehtaa et al., 2008). Interestingly, it has been shown that
poorly differentiated adenocarcinomas tend to develop more fre-
quently in severely anthracotic lungs, and that well-differentiated
adenocarcinomas progress more readily to less differentiated tu-
mours (Wang et al., 2003).
Although primary lung cancer is rare in dogs, accounting for
approximately 1% of all canine tumours (Withrow, 2007), the inci-
dence is increasingly reported. The trend has been attributable to
environmental changes, such as enhanced pollution, but also to
improved diagnostic procedures, greater availability of necropsy
data and increased pet longevity (Moulton, 1990). Previous studies
have raised the question as to whether human factors such as

1090-0233/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tvjl.2009.09.004
 G. Bettini et al. / The Veterinary Journal 186 (2010) 364–369
passive cigarette smoking and/or urban living are related to lung
cancer in dogs (Leake, 1961; Auerbach et al., 1970; Reif and Cohen,
1971; Ogilvie et al., 1989; Reif et al., 1992; Coggins, 2001; Hecht,
2005), but a causative role has not been definitely shown. Further-
more, the relationship between deposition of black dust matter in
lungs (anthracosis) and primary pulmonary carcinoma has not
been investigated in dogs. The objective of this study was to inves-
tigate in a series of canine lungs whether there was a demonstrable
association between the quantity of anthracosis and the frequency
of cancer.
Material and methods
Dogs with primary lung tumour
Records of dogs with suspected primary lung tumour were extracted from the
necropsy database (1980–2005) of the Pathology Division of the Department of Vet-
erinary Public Health and Animal Pathology, University of Bologna.
Histological examination was performed on haematoxylin–eosin (HE) stained
sections retrieved from the archive (formalin fixed and paraffin embedded speci-
mens) in order to confirm the primary origin and to characterise the histotype, in
accordance with World Health Organization guidelines (Dungworth et al., 1999).
If doubt arose, immunohistochemistry was applied to exclude metastatic lung tu-
mours using appropriate antibodies. In addition, primary tumours were graded
according to the scheme proposed by McNiel et al. (1997) which is based on degree
of differentiation, nuclear pleomorphism, mitotic activity, nucleolar size, fibrosis,
necrosis, and demarcation.
Tumour staging was based on reported clinical and pathological findings,
according to the tumour-node-metastasis (TNM) system (Owen, 1980) as follows:
T1, solitary tumour surrounded by lung or visceral pleura; T2, multiple tumours
of any size; T3, tumour invading neighbouring tissues; N0, no evidence of lymph
node involvement; N1, neoplastic lymph node involvement; M0, no evidence of
metastases; M1, metastases present. For examination of anthracosis, histological
sections comprising both tumour tissue and normal lung (at least one section from
the cranial lobe and one from the central portion of the caudal lobe) were selected.
Control animals
Histological samples from adult dogs that had died during the same period
(1980–2005) and affected by any disease (including cardiac and respiratory disor-
ders, but excluding primary lung tumours) were extracted from the necropsy
Fig. 1. Examples of anthracosis scoring in canine lung samples, HE stain, magnification 40; scale bars 300 lm. (a) Score 0, no dust is seen; (b) score 1, minimal amount of
dust, but sufficient to note its presence; (c) score 2, moderate amount of dust; (d) score 3, multiple large or many small dust particles accumulated.
365
database and served as controls. Because the study spanned 25 years, the number
of controls from each year was generally proportional to the dogs with pulmonary
cancer. Inclusion criteria included adequate signalment information (breed, age,
sex) and availability of lung sections; all animals that met the criteria were in-
cluded. If lesions were diffuse or not evident, one specimen from the cranial lobe
and one from the caudal lobe were routinely collected; if lesions were focal, affected
areas and unaffected lung parenchyma from the above areas were sampled. The left
or right side was selected for sampling where post mortem hypostasis, if present,
was less evident. HE stained sections prepared as previously outlined (fixation in
formalin, embedding in paraffin) were examined to achieve a diagnosis. Samples
were excluded if lung morphology was not preserved (e.g., autolysis).
Evaluation of anthracosis
In order to achieve homogenous staining, new 4 lm sections were cut from par-
affin blocks, and stained with HE. Lung anthracosis was identified if a black granular
or grey translucent particulate material was evident within alveolar and interstitial
macrophages, or extracellularly, adjacent to bronchioles or within the interalveolar
interstitium.
The amount of anthracosis was scored according to Schoning et al. (1996) as fol-
lows: score ‘0’ if no particulate material was seen; ‘1’ if a minimal quantity was
noted, just sufficient to reveal its presence; ‘2’ if a moderate quantity was observed,
and ‘3’ where either multiple large or many small dust had accumulated (Fig. 1).
The histological appearance of inhaled dust and their birefringence under polarised
light were also evaluated, because grey filamentous birefringent particles are indic-
ative of a siliceous content (Day et al., 1996).
Anthracosis was classified as ‘A’ if the particulate material was visible as black
granular opaque pigment, ‘B’ if the particulate material appeared grey translucent
and needle-like, and ‘AB’ if a combination of the two patterns was observed
(Fig. 2). When examined under polarised light, birefringence of anthracosis was
scored as ‘POL-0’ if no birefringent particles were present, ‘POL-1’ if part of the accu-
mulated particulate material showed mild-to-moderate birefringence, or ‘POL-2’ if
the entire dust deposits showed marked birefringence (Fig. 3).
Statistical analyses
We investigated factors associated with the development of lung cancer, the
association between lung tumour-related variables and anthracosis, and the associ-
ation between age of dogs and the amount of anthracosis. In particular, the amount,
appearance and birefringence of anthracosis, in addition to age, sex and breed (i.e.,
brachycephalic and dolichocephalic), were studied to assess whether they are asso-
ciated with the development of lung cancer (i.e., dependent variable) in dogs using
univariate logistic regression. Among the independent variables, the amount of
366 G. Bettini et al. / The Veterinary Journal 186 (2010) 364–369

Fig. 2. Examples of different histological appearance of anthracosis in canine lung samples, HE stain, magnification 400; scale bars 30 lm. (a) ‘A’ anthracosis, black granular
opaque pigment; (b) ‘B’ anthracosis, grey translucent needle-like particles; (c) ‘AB’ anthracosis, association of ‘A’ and ‘B’ anthracosis.

Fig. 3. Examples of birefringency under polarised light of dust particles in canine lung samples, HE stain, magnification 400; scale bars 30 lm. (a) ‘POL-0’, no birefringent
particles; (b) ‘POL-1’, mild birefringency; (c) ‘POL-2’, marked birefringency.

anthracosis and age were considered as continuous variables, whereas appearance
and birefringence of anthracosis, sex and breed were considered as dichotomous.
Factors which on univariate analysis had P < 0.20 were further used to evaluate
them in a multivariate logistic regression model. The odd ratio (OR) and 95% confi-
dence interval were calculated.
In the group of dogs with lung cancer, tumour histotype, malignancy grade, and
TNM stage, were analysed to identify possible associations with the amount,
appearance and birefringence of lung anthracosis. Contingency tables were used
for analysis. For the above variables, categories represented by less than five cases
were not considered. To assess whether older dogs had higher amounts of dust in
the pulmonary parenchyma, age was compared among scores ‘0’, ‘1’, ‘2’ and ‘3’ of
anthracosis in control animals, with one-way ANOVA followed by Tukey’s multiple
comparison. Significance was considered at P < 0.05. Statistical analyses were con-
ducted using SPSS, Version 10.0.
Results
Dogs with primary lung tumour
Sixty-four dogs with a post mortem diagnosis of supposed pri-
mary lung tumour were initially selected. Of these, 29 were
excluded after careful review of the necropsy reports and histolog-
ical slides because the gross diagnosis of primary pulmonary can-
cer was not confirmed (metastases from nine mammary gland
carcinomas, four histiocytic sarcomas, three chemodectomas, three
multicentric lymphomas, two haemangiosarcomas, one each of
haemangiopericytoma, fibrosarcoma, malignant peripheral nerve
sheet tumour, chondrosarcoma, Sertoli cell tumour, thyroid carci-
noma, ovarian carcinoma and bronchial hamartoma).
In the remaining 35 dogs with a diagnosis of primary lung tu-
mour, the mean age was 10.6 years (range 5–18 years), and there
were 17 (48.6%) males and 18 (51.4%) females. Breed distribution
was as follows: six dogs (17.1%) were German shepherds, four
(11.4%) were English setters, and each of nine other dogs belonged
to individual breeds. The remaining 16 dogs (45.7%) were cross-
bred. There was only one brachycephalic dog (a Boxer).
The 35 primary lung tumours were classified histologically with
16 (45.7%) being papillary adenocarcinomas, 11 (31.4%) bronchiolo-
alveolar carcinomas, two (5.7%) squamous carcinomas, two (5.7%)
adenosquamous carcinomas, two (5.7%) large-cell carcinomas,
 G. Bettini et al. / The Veterinary Journal 186 (2010) 364–369 367

Fig. 4. Examples of primary cancer in canine lung samples, HE stain, magnification 100; scale bars 200 lm. (a) Papillary adenocarcinoma; (b) bronchiolo-alveolar
carcinoma; (c) bronchial gland carcinoma; (d) adenosquamous carcinoma.

one (2.9%) acinar adenocarcinoma and one (2.9%) bronchial gland
carcinoma (Fig. 4).
The histological grading yielded eight (22.9%) grade I tumours,
21 (60.0%) grade II and six (17.1%) grade III. At necropsy, eight
(22.9%) dogs were staged as T1N0M0. The remaining were staged
as T2N1M0 (n = 6), T2N0M0 (n = 5), T1N1M1 (n = 5), T3N0M1 (n = 2),
T2N1M1 (n = 2), T3N0M0 (n = 1), T2N0M1 (n = 1), T3N2M1 (n = 1); for
one dog, M was not available (T1N0Mx), whereas for three dogs
information was not gathered concerning either N or M (T1NxMx).
Overall, 13 (40.6%) dogs had stage I disease (local disease), seven
(21.9%) stage II (node-positive disease), and 12 (37.5%) stage III (lo-
cally invasive disease and/or distant metastases, or distant lymph
node involvement). Distant metastatic sites for dogs with M1 were
liver, kidney, pancreas, heart, central nervous system and stomach.
Anthracosis was evident in the normal background lung of all
primary lung tumours, and the amount was scored as ‘1’ in three
(8.6%) cases, ‘2’ (40%) in 14 cases and ‘3’ (51.4%) in 18 cases (Ta-
ble 1). None had score ‘0’. The histological appearance of anthraco-
sis was classified as ‘A’ in 19 (54.3%) cases, ‘B’ in 2 (5.7%) cases and
‘AB’ in 14 (40%). Particle birefringency under polarised light was
mild-to-moderate in 18 cases (POL-1, 51.4%) and marked in nine
(POL-2, 25.7%); in eight cases there was no birefringency (POL-0,
22.9%). In 18 cases (51.4%) anthracosis was also evident within
the tumour as well as in the surrounding normal lung tissue.

Table 1 Control animals

Histological scoring of lung anthracosis in 35 dogs with a primary lung tumour and in
160 controls.
One hundred and sixty canine lungs were retrieved for analysis.
Dogs with primary lung tumour (n = 35) Control dogs (n = 160) The mean age of the dogs was 8.9 years (range 3–16 years). There
Dust score were 77 males (48.1%) and 83 females (51.9%). Thirty-eight dogs
Score 0 0 2 (1.25%) (23.8%) were German shepherds, 24 (15%) English setters, 10
Score 1 3 (8.6%) 51 (31.9%)
(6.2%) Boxers, eight (5%) were Cocker spaniels, seven (4.4%) English
Score 2 14 (40%) 65 (40.6%)
Score 3 18 (51.4%) 42 (26.25%) pointers, four (2.5%) Deutsch kurzhaars, three (1.9%) Schnauzers
Dust type
and three (1.9%) Italian spinones. Twenty-six dogs (16.3%) be-
Type A 19 (54.3%) 104 (65%) longed to individual breeds, and 37 (23.1%) were cross-bred. If
Type AB 14 (40%) 38 (23.75%) grouped according to their morphotype, 150 dogs (93.7%) were
Type B 2 (5.7%) 18 (11.25%) dolicocephalic breeds and 10 (6.3%) brachycephalic.
Birefringence Lung histopathology demonstrated lesions in 106/160 lungs
POL-0 8 (22.9%) 49 (30.6%) (66.2%), represented by secondary tumours (n = 44), acute or
POL-1 18 (51.4%) 65 (40.6%)
chronic pneumonia (n = 20), alveolar oedema (n = 16), emphysema
POL-2 9 (25.7%) 46 (28.8%)
(n = 10), compressive atelectasis (n = 10), chronic passive conges-
Dust score: 0, no particulate material; 1, minimal quantity just sufficient to reveal its tion (n = 4), metastatic calcification (n = 1) and pulmonary vein
presence; 2, moderate quantity; 3, multiple large or small dust accumulates. Dust
thrombosis (n = 1). In the remaining 54 dogs, lung histology was
type: A, black granular opaque pigment; B, grey translucent needle-like particles;
AB, combination A and B patterns. Birefringence (under polarised light): POL-0, no
unremarkable. Lung anthracosis was evident in almost all lung
birefringent particles; POL-1, mild-to-moderate partial birefringency; POL-2, dif- specimens of control dogs, but the amount varied among samples
fuse marked birefringency. (anthracosis score ‘0’: 1.25%; score ‘1’: 31.9%; score ‘2’: 40.6%; and
368 G. Bettini et al. / The Veterinary Journal 186 (2010) 364–369
score ‘3’: 26.25%). With regards to the histological appearance of
anthracosis type, the majority of pulmonary specimens (65%)
was classified as ‘A’, whereas type ‘B’ and ‘AB’ accounted for
11.3% and 23.7%, respectively (Table 1).
When lung anthracosis was observed under polarised light, 30.6%
of cases did not show any birefringent particles (POL-0), 40.6% were
scored POL-1 and 28.8% as POL-2. Birefringence of dust particles was
far more evident when anthracosis was of B or AB type. Indeed, 15/18
cases of ‘B’ anthracosis were scored POL-2 (83.3%) and three were
POL-1 (16.7%), and 22/38 cases of ‘AB’ anthracosis were scored
POL-2 (57.9%) and 16 were POL-1 (42.1%). Conversely, of 104 cases
of ‘A’ anthracosis, nine were scored POL-2 (8.7%), 46 were POL-1
(44.2%), and 49 were POL-0 (47.1%).
Statistical analyses
Using univariate analysis the amount and appearance of anthra-
cosis, and age were associated with lung cancer but not birefrin-
gence of anthracosis and sex. The confounding effect of
brachycephalic or dolichocephalic breed on tumour development
was not assessed due to the low number of brachycephalic dogs
(one dog in the lung cancer group, ten in the control group). Mul-
tivariate analysis revealed an increased risk of lung cancer devel-
opment in dogs with a higher amount of pulmonary anthracosis
(OR: 2.11, CI 95%: 1.20–3.70; P < 0.01). The histological appearance
of anthracosis and age were not associated with lung cancer.
Relationships were not observed between the tumour histo-
type, including papillary adenocarcinoma and bronchiolo-alveolar
carcinoma, histological grade or TNM stage, and the amount,
appearance and birefringency of lung anthracosis. Associations
were not analysed for squamous carcinoma and large-cell carci-
noma because there were less than five cases. In control dogs, ani-
mals with a lung anthracosis score of ‘3’ were significantly older
than those with a score of ‘1’ (mean age, 10.1 vs. 7.9 years;
P < 0.001) but not than those with score ‘2’ (mean age, 8.9 years).
Scores of ‘0’ were not included in the analysis because there were
only two cases.
Discussion
The purpose of the present study was to determine in a series of
canine lungs affected or not by primary lung cancer whether there
was a relationship between cancer and anthracosis. We found evi-
dence that the amount of anthracosis due to inhalation of polluted
air was associated with a higher frequency of lung cancer.
Primary lung tumours are uncommon in animals when com-
pared to humans, but relatively more frequent in dogs than in
other animal species (Caswell and Williams, 2007). Studies carried
out in dogs have suggested that environmental carcinogens,
including atmospheric pollution and tobacco smoke, may enhance
the risk of lung tumours, but a definitive association has not yet
been demonstrated (Leake, 1961; Ogilvie et al., 1989; Auerbach
et al., 1970; Reif and Cohen, 1971; Reif et al., 1992). Additionally,
a higher incidence of lung tumours has been observed in brachyce-
phalic breeds possibly due to reduced nose filtration ability (Reif
et al., 1992).
Although smoking is the major cause of lung cancer in people,
large case-control studies have shown that air pollution per se is
a risk factor for lung cancer mortality, and that there is a significant
association between exposure to road traffic and lung cancer inci-
dence in non smokers (Subramanian and Govindan, 2007; Beelen
et al., 2008).
Pulmonary anthracosis is commonly observed in canine lung
specimens, and is considered as an incidental finding in city-dwell-
ing animals or in those cohabiting with smokers (Calderón-Gar-
cidueñas et al., 2001; Caswell and Williams, 2007). In addition to
anthracosis, dogs can also be affected by silicate pneumoconiosis,
which appears as crystalline translucent and birefringent needle-
like particles in pulmonary macrophages (Day et al., 1996; Caswell
and Williams, 2007), acting as irritant and inducing lung fibrosis.
Silicate pneumoconiosis is expected to derive mainly from the geo-
logic environment (Day et al., 1996) but classic anthracosis and
pneumosilicosis can also coexist (anthrasilicosis) (Balchum et al.,
1963; Day et al., 1996). Owing to its frequency and assumed unim-
portance, anthracosis is generally ignored in routine histopathol-
ogy (Schoning et al., 1996); conversely, pneumosilicosis is
considered clinically important, and reportedly associated with
extensive areas of lung fibrosis containing multifocal granuloma-
tous infiltrates (Canfield et al., 1989; Day et al., 1996; Caswell
and Williams, 2007). Furthermore, canine anthrasilicosis has been
reported to increase linearly with age (Schoning et al., 1996).
We found that almost all dogs had a considerable amount of
anthracosis. Lung histopathology of control dogs prompted a wide
range of pulmonary lesions in two-thirds of the animals, but there
was no evidence of a connection between these lesions and anthra-
cosis, as neither fibrosis nor granulomatous infiltrates were evi-
dent even in heavily anthracotic lungs. The slight relationship in
dogs of our series between the amount of dust deposited in lungs
and the age may be related to the fact that dogs, although from the
same geographic area, did not share strictly similar environments
whereas the study that demonstrated a linear correlation between
age and lung anthracosis was carried out on a series of racing Grey-
hounds which had been living and trained in the same, dusty, envi-
ronment (Schoning et al., 1996).
In agreement with previous data (Ogilvie et al., 1989; Ramos-
Vara et al., 2005; Polton et al., 2008), the series of 35 primary lung
tumours included in the present study showed that affected dogs
were mostly older than 10 years and of either sex. Of note, almost
one-third of the dogs with a primary epithelial lung tumour were
German shepherd dogs or Irish setters. However, these two breeds
were also highly represented in the control group. With regard to
tumour histotype, a predominance of papillary adenocarcinoma
and bronchiolo-alveolar carcinoma was observed. Based on micro-
scopic examination, anthracosis was evident in the surrounding
normal lung in all cases.
Notably, the amount of background anthracosis was signifi-
cantly associated with lung cancer; in particular, the increasing
grade of anthracosis augmented the odds of tumour formation by
2.11-fold (CI 95%: 1.20–3.70; P < 0.01), possibly suggesting a rela-
tionship. This relationship has been previously observed in humans
(Hou et al., 1998; Pope et al., 2002; Mehtaa et al., 2008) and has
been mostly linked to the numerous direct and indirect DNA dam-
aging agents carried by combustion derived particles (PM2.5).
These small sized particles are known to cause a variety of molec-
ular events and inflammatory responses once accumulated in lung
tissues that may eventually trigger carcinogenesis. Histological
appearance and birefringence were not associated with lung
cancer in line with the assumption that carcinogens are stuck to
combustion-derived black particles, rather than to birefringent
soil-derived particles containing silicates.
The retrospective nature of the study may have partly biased
the results. In particular, although dogs with lung cancer and con-
trol dogs came from the same geographical area, we cannot rule
out that the former group may have been exposed to different pol-
lutants other than through breathing. Thus, the observed associa-
tion between anthracosis and lung cancer may simply be
incidental. Nevertheless, we endeavoured to reduce bias by select-
ing control animals proportional for the year of death to those with
lung cancer, and by accounting in the analysis for the confounding
effects of age and sex. However, the influence of specific breeds or
morphotype was not assessed.
 G. Bettini et al. / The Veterinary Journal 186 (2010) 364–369
In humans with lung cancer, a severe degree of anthracosis has
also been linked to poor prognosis (Wang et al., 2003). This was not
confirmed in our samples, as there was no relationship between
the amount of anthracosis and tumour grade, or TNM stage. This
may be due to the relatively small sample size or to the retrospec-
tive nature of the study. Furthermore, dogs diagnosed with a lung
carcinoma are often euthanased, thereby precluding follow-up
studies during which a well-differentiated carcinoma might switch
to a less differentiated phenotype.
Conclusions
We have shown an association between pulmonary anthracosis
due to inhalation of polluted air and lung cancer in dogs. Even
though a causal relationship cannot be definitely proved, we pro-
pose that, similar to humans (Hou et al., 1998; Pope et al., 2002;
Beelen et al., 2008), chronic accumulation of dust in the pulmonary
parenchyma contributes to tumour development. Further studies
are required to characterise the specific environmental contami-
nants which may be responsible for lung carcinogenesis in dogs.
Conflict of interest statement
None of the authors of this paper has a financial or personal
relationship with other people or organisations that could inappro-
priately influence or bias the content of the paper.
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