Page 35 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

14 PART I The Biology and Pathogenesis of Cancer

B-cell subtype T-cell subtype
B-cell lymphomas T-cell lymphomas All lymphomas
VetBooks.ir All

Golden
Golden
Cocker
Spaniel Retriever Boxer Retriever significant 3 5 66 51 19 17 7 70
genes
Boxer
Samples 10 54 16 25 Cocker Golden T-cell
Spaniel Golden Retriever B-cell
Retriever
Average 628 412 630 444
mutations
Top 5
significant 3 2 3 5 5 5 5
Avg. nonsilent genes
variants 17.4 14.6 22.8 22.9 Cocker Golden Boxer Golden T-cell B-cell
Spaniel Retriever Retriever
Total significant 8 71 6 20
genes
A B
• Fig. 1.8 Next generation sequencing of tumor and normal exomes for canine lymphoma in three breeds.
(A) Sample numbers and average mutations per breed and immunophenotype. (B) Overlap of significantly
mutated genes between lymphoma types. Left panel, The two B-cell lymphoma-predisposed breeds
share some of their most significantly mutated genes. Center panel, The two T-cell lymphoma-predis-
posed breeds do not share any top significantly mutated genes. Right panel, Some overlap in significantly
mutated genes can be seen between all the B-cell lymphomas and all the T-cell lymphomas. (Reproduced
with permission from Elvers I, Turner-Maier J, Swofford R, et al. Exome sequencing of lymphomas from
three dog breeds reveals somatic mutation patterns reflecting genetic background. Genome Res. 2015
Nov;25(11):1634-1645. https://doi.org/10.1101/gr.194449.115. Figs. 1.1A and 1.2.)
document is now required by law to be released every 2 years by the showed only a weak relationship between living with a smoker and
Secretary of the Department of Health and Human Services. The the development of lung cancer, and the risk did not increase with
fourteenth edition of the RoC, released in 2016, lists 248 potential an increased smoke exposure index. 152 Additionally, a more recent
carcinogens, of which 61 are categorized as known to be human case-control study found no association between secondhand
carcinogens, and 186 are categorized as reasonably anticipated to smoke and primary lung cancer in dogs. 153 However, an associa-
be human carcinogens. 146,147 Five of the seven additional carcino- tion between environmental tobacco smoke (ETS) and nasal can-
gens were viruses: Epstein-Barr virus, human immunodeficiency cer in dogs, especially in dolichocephalic breeds, was supported in
virus (HIV) type 1, human T-cell lymphotrophic virus type 1, a case-control study that ran from 1986 to 1990. 154
Kaposi sarcoma–associated herpesvirus, and Merkel cell polyoma- Based on human data suggesting that smoking may increase
virus. Although no such report exists for companion animals, one the risk of non–Hodgkin lymphoma, 155,156 Bertone et al exam-
could reasonably assume that there would be considerable overlap ined the relationship between ETS exposure and the development
between such a list and the potential carcinogens found in the RoC. of feline lymphoma. 157 In a case-control study of 80 cats with
Although the list of carcinogens reportedly associated with cancer in malignant lymphoma and 114 control cats with renal disease that
companion animals is less extensive, this section addresses chemical, presented between 1993 and 2000, the relative risk of lymphoma
physical, and hormonal factors that have been linked to carcinogen- for cats with any household ETS exposure was 2.4. As reported for
esis in pet animals. Viral carcinogenesis is addressed in a separate male smokers, 158 the risk of lymphoma increased with increases
section (see Section C later in the chapter). Additionally, more in- in either duration or quantity of exposure. More recently, an Ital-
depth information regarding the epidemiology of cancer, and the ian study of waste management and cancer in companion animals
strength of evidence for these factors, is addressed in Chapter 4 (see demonstrated that ETS exposure significantly increased the risk of
Tables 4.4 and 4.5, specifically). the development of lymphoma in dogs. 159
Hypothesizing that inhalation and ingestion of carcinogens in
Chemical Factors ETS during grooming might predispose cats in smoking house-
holds to the development of oral squamous cell carcinoma (SCC),
Environmental Tobacco Smoke Bertone et al examined ETS and other environmental and lifestyle
risk factors in cats with SCC. 160 Exposure to ETS was associated
In people tobacco use continues to be one of the leading causes of with a twofold, but statistically insignificant, increased risk of oral
mortality worldwide; an estimated 1 billion deaths could be pos- SCC. 160 In a separate report the investigators found positive asso-
sible in the next century. 148 Cancers currently recognized by the ciations between ETS and p53 overexpression; however, the find-
US Surgeon General as being caused by smoking include lung, ings again were not statistically significant. 161 Loss of wild type
esophagus, bladder, pancreas, and other cancers. 149 Of course, p53 and/or gain of mutant p53 function have been shown to be
animals are not likely to be primary smokers, but they do share critical to carcinogenesis from tobacco exposure in human lung
our environment and can commonly be exposed to secondhand cancer. 162 The aforementioned suggestion that both ETS and p53
smoke. Despite ample evidence that secondhand smoke increases mutations might play a role in the etiology of feline oral SCC is
the risk of lung cancer in people, 150,151 the data for this effect intriguing. The study of other genetic mutations 163 and epigen-
in companion animals is less compelling. One case-control study etic aberrations 164 in tumor-bearing animals with ETS exposure
involving dogs with lung cancer from two veterinary hospitals is warranted.