Page 40 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 1 The Etiology of Cancer 19

tumor than intact dogs. For each additional month of being adrenal gland. 270 Most of these tumors in male dogs resolve after
intact, a 1.4% reduction in tumor risk was noted. 265 OSA also castration, a fact that lends further support to the assertion that
androgens are involved in the etiology of this tumor (see Chapter
was evaluated in the aforementioned Davis study of more than
VetBooks.ir 90,000 dogs. 263 Both spayed female and neutered male dogs had 23). 271
a significantly increased risk of having OSA, OR 2.53 and 1.62,
respectively, compared with intact animals. The authors did theo- Prostate Cancer
rize that this increased risk could be associated with greater lon-
gevity in neutered dogs. 263 Although a well-established link exists between the presence of
testosterone and the development of benign prostatic hyperpla-
Hemangiosarcoma sia (BPH) in dogs and man, prostatic cancer risk is not higher
in intact dogs compared with those that are castrated. 272 To the
A highly aggressive and almost uniformly fatal neoplasm, hem- contrary, neutered dogs have been shown to be at increased risk.
angiosarcoma (HSA) is diagnosed more frequently in dogs than Castration is likely not an initiating event, but it is thought to
in any other species, with breed predilections in retriever breeds favor tumor progression. 273–276 A clear relationship between age
(see Chapter 34). The aforementioned breed-specific studies 261,262 at castration and the risk of prostate cancer development has yet
reported an increased risk for HSA development in spayed female to be determined (see Chapter 29).
dogs compared with intact female dogs. Female golden retriev-
ers spayed after 1 year of age were diagnosed with HSA four
times more frequently than intact female dogs, or dogs spayed SECTION C: CANCER-CAUSING VIRUSES
“early.” 261 Of note, only overall percentages of disease incidence
were reported; statistical analysis of those percentages and subse-
quent p-values were not available. The authors did not report a DENNIS W. MACY
difference in neuter status and HSA development in male golden
retrievers. 261 Spayed Vizsla dogs were nine times more likely than Both DNA- and RNA-containing viruses are known to cause can-
intact females to develop HSA. 262 As in the golden retriever study, cer. An initial step in malignant transformation of normal cells
no difference in intact or neutered males was noted. In the large by most tumor viruses is the integration of all or part of the viral
UCD retrospective study, neutered female and male dogs were DNA (or DNA copy of retroviral RNA) into the host cell genome.
at increased risk (ORs 3.18 and 1.39, respectively) of developing For some viruses specific viral genes (oncogenes) have been iden-
HSA compared with their intact counterparts. 263 Also at UCD, tified that lead to malignant transformation when expressed in
an association between age of cancer-related mortality and gonad- normal cells. Other viruses, through the process of integration,
ectomy in golden retrievers was explored. 266 Goldens available for enhance or repress the expression of normal cellular genes, result-
a necropsy examination from 1989 to 2016 were included. HSA ing in cellular transformation or uncontrolled growth. 277
was the most common cause of cancer-related death in this breed.
Although a greater proportion of spayed female dogs died of can- Tumor-Causing Viruses of Dogs
cer, their overall life span (9.83 years) was significantly longer than
dogs that died of non–cancer-related causes (6.93 years). 266 The Papillomaviruses
authors concluded that age had a larger effect on cancer-related
mortality than reproductive status. Papillomaviruses are potentially oncogenic, contagious, and infec-
278
tious and have been described in wild and domestic animal species.
Mast Cell Tumors Papillomaviruses are considered relatively species specific, and isolates
278
of humans, cattle, and dogs lack serologic cross-reactivity. How-
Breed predilections for mast cell tumor (MCT) development have ever, cross-infection with other species can occur. For example, the
been reported, but a gender predilection in this neoplasm appears coyote can be infected with dog isolates, and bovine papillomaviruses
279
to be lacking (see Chapter 21). Again, in the retrospective study of type 1 and type 2 have been reported to infect horses. In addition,
90,000 dogs at UCD, spayed female and neutered male dogs were bovine papillomaviruses have been isolated from tumors in cats, indi-
at an increased risk for MCT development compared with intact cating a unique cross-species infection in a dead-end host. 280
dogs. 263 Mirroring the findings for previously described cancers, Sixteen papillomaviruses from three different genera infect dogs
spayed female dogs seemed to have the highest risk of MCT devel- and are responsible for a wide spectrum of clinical syndromes—
opment. This phenomenon is reflected in golden retrievers and canine papillomavirus (CPV)-1, oral papillomas; CPV-2 and -6,
Vizslas. 261,262 In a case-control study of 252 dogs with MCTs, an cutaneous papillomas and cutaneous pigmented plaque. CPV-3, -4,
increased risk for development was found in spayed female dogs -7, -8, -9, -10, -11, -14, -15, -16 are papillomaviruses of the family
(OR 4.1). 267 Despite the repeatable finding of increased risk in Papovaviridae; they produce benign, mucocutaneous and cutaneous
spayed female dogs, the influence of hormones in canine MCTs canine papillomas and in rare cases transform into squamous cell
remains unclear. Conflicting evidence exists on the presence of carcinoma. 281,282,403
estrogen receptors in canine MCTs. 268,269 The canine papillomaviruses are naked (e.g. non-enveloped)
DNA viruses; they are larger than the canine parvoviruses but
Perianal Adenoma similar in structure. In vitro propagation methods are not used
to identify the virus, but electron microscopy has been used to
Perianal adenoma is androgen dependent and occurs primarily in detect the virus in infected tissues. Other methodologies with
intact male dogs, whereas perianal adenocarcinoma occurs in both varying sensitivity and specificity, such as Southern blot hybrid-
intact and castrated males. Perianal adenomas also may develop in ization, dot blot, and reverse hybridization, have been used more
female dogs secondary to androgenic hormone secretion from the recently to identify the virus. Although considered less sensitive,