By Brennen McKenzie, MA, MSc, VMD, cVMA

One of the most common and dreaded diseases we see in small-animal patients is malignant neoplasia. While the data on exactly how many dogs and cats get cancer is complex and uncertain,¹ there is no doubt it is common, especially in older animals.

It is often stated one out of four or even one out of three dogs will eventually get cancer, and perhaps one in five cats. The source for this estimate is hard to track down, and there is likely significant variation depending on region, breed, and other variables. However, clearly cancer is a significant cause of illness and death in companion animals.

There is no single reason why so many dogs and cats get cancer. It is rarely even useful to think of cancer in terms of single causes, since neoplastic transformation, and the survival and spread of neoplastic cells is a complex process, typically requiring multiple events at many different levels to occur.

Genetic and epigenetic factors may predispose to dysregulated cell proliferation or may impede the action of tumor-suppressing mechanisms. Environmental factors may further encourage the growth of cancer and damage an animal's defenses. As clinicians and pet owners, we are better off thinking in terms of risk factors than causes. This helps us focus on which risk factors can potentially be modified to make cancer less likely to harm the health of our patients and pets.

There are a number of strategies that have proven effective in reducing cancer incidence in humans. Many of these may also be beneficial for companion animals, though often we lack the research evidence to demonstrate the true value of particular approaches. Judicious extrapolation from evidence in humans and lab animals is a necessary evil in veterinary medicine, and currently it is the foundation upon which we must build rational cancer prevention strategies.

The interventions we should consider fall into two broad categories: elimination of identifiable root cause for specific cancers, and general reduction of risk for one or more cancers through interventions that address contributory causes.

Elimination of specific causes

There are few cancers for which a single predominant cause can be identified and eliminated. Realistically, even variables that greatly increase the incidence of specific cancers usually explain only a portion of the variance in cancer occurrence between groups, and elimination of these variables may, at best, greatly reduce the occurrence of specific neoplasms without eliminating them entirely.

An example of this in human medicine would be cervical cancer attributable to human papilloma virus (HPV). Ninety percent of cervical cancers in women are caused by four varieties of HPV. Studies have shown vaccinating girls to protect against HPV not only prevents infection and dysplasia of cervical cells, but can prevent up to 90 percent of cervical cancers compared to the rate in unvaccinated women.² Other cancers caused by infection, such as liver cancer due to hepatitis B, are similarly greatly reduced by prevention of infection with the causal organism.

There are a few examples of similar benefits to prevention of infection-associated cancer in animals, notably the reduction in cases of lymphoma or leukemia caused by feline leukemia virus (FeLV) following the introduction of FeLV vaccines (though, unfortunately, the disease remains common due to other causes).³

Other than a few infectious agents, there are not many discrete variables that can be considered the root cause of specific cancers. Even a clear villain like cigarette smoking is responsible for about 60 to 90 percent of lung cancers, and for a lesser share of the risk for other types of cancer.^4,5 Reducing or eliminating smoking in an individual can potentially reduce lung cancer risk dramatically.

Efforts on a population level to prevent cancer by reducing smoking have been very successful, though the realized benefits are less than the potential benefits due to incomplete efficacy of efforts to change behavior.^6-8 However, as many as 20 percent of people who never smoke will still get lung cancer due to other causes.

Meanwhile, in dogs and cats, few environmental exposures have been shown to be clear, avoidable causes of specific cancers. There is weak evidence second-hand tobacco smoke and a variety of chemicals can increase the risk of various cancers in pets, but the data are too tenuous to suggest avoidance of these agents would prevent or dramatically reduce these cancers.^9-18 Avoidance of such exposures is a reasonable precaution, of course, but these fit more properly into the category of modifiable risk factors than specific causes.

Modification of risk factors

The most common overall strategy in humans for reducing cancer risk is to combine avoidance of as many potential risk factors as possible with implementation of multiple protective interventions. This is, in many ways, less psychologically satisfying than identifying and eliminating a single "cause" of cancer, but it reflects the biological reality of neoplasia much more accurately, and it is currently the most effective approach.

Many modifiable risk factors for cancer in humans are also risk factors for other diseases, and cancer prevention is part of a broader integrated preventative health practice. Obesity, for example, is probably the single greatest contributor to cancer in humans after cigarette smoking. Obesity has been linked to as many as 13 types of human cancer, and it may be a major causal factor in as much as 20 percent of cancer cases.^19-22 Weight reduction appears to reduce both cancer incidence and mortality.^23,24

Obesity is, of course, a serious problem in companion animal medicine as well.^25-26 The data are less reliable and robust for dogs and cats than for humans, but there is some evidence to suggest obesity increases the risk of certain cancers in these species.^27-29 Obesity is certainly a cause of chronic inflammation and peripheral insulin resistance, both of which are solidly linked to neoplasia in humans and lab animals, so there is no reason to doubt this condition raises cancer risk in pets as well.

Though there is no specific evidence showing weight reduction in dogs and cats reduces cancer risk, it is likely this will turn out to be one of the most important and effective means of reducing overall cancer risk available to pet owners.

There is also good evidence suggesting other so-called "lifestyle modifications" reduce cancer risk in humans. Apart from reducing smoking and obesity, reduction in alcohol consumption, increase in physical activity, and adherence to dietary recommendations (such as eating more vegetables and whole grains, and limiting fat, meat, and consumption of highly processed foods) all reduce cancer risk in humans.^30-34 While some of these may not be relevant to companion animals (such as alcohol consumption guidelines), it is plausible increased physical activity and some nutritional strategies could reduce cancer risk.

Unfortunately, there is very little direct evidence identifying specific interventions and their effect on cancer risk in our pets. Exercise, for example, is almost certainly beneficial, but what type, how much, how often, and many other questions about specific physical activity guidelines remain a matter of pure speculation.

Similarly, efforts have been made to connect evidence about the relative health effects of fresh and packaged foods in humans to the risks of commercial pet diets in dogs and cats. This is very much a comparison of apples to oranges, since a well-formulated and produced kibble is something quite different from a bag of potato chips or a hot dog.

I remain sympathetic to the hypothesis that fresh, whole foods may have health benefits in companion animals, but I also remain skeptical of specific claims and recommendations until there is some real evidence to guide us. Proponents of every alternative feeding strategy, from fresh-cooked to raw to keto to vegetarian, claim the diets they support can prevent cancer, but there is no reliable direct evidence to support such claims.^35-40

Another cancer-prevention tool validated in humans, which may have the potential to protect some dogs and cats against cancer, is sunscreen. A number of neoplastic and non-neoplastic skin conditions are associated with sun exposure in dogs and cats, especially in those with light-colored skin and coats.^41,42 Theoretically, sun protection should reduce the risk of these cancers as it does in humans.

There is little research, however, on the actual benefits of specific strategies for protecting companion animals against solar radiation, and unfortunately, many of the products marketed for this purpose may not have the efficacy claimed.^43,44

A common cancer-prevention strategy employed in dogs and cats not routinely used in humans is neutering. Neutering clearly prevents testicular, ovarian, and uterine neoplasia, and likely also reduces the risk of mammary neoplasia in females.⁴⁵ However, neutering may also raise the risk of other types of neoplasia, and the precise balance of risks and benefits varies between sexes, breeds, and individuals in ways difficult to predict.⁴⁵

Finally, the most important risk factor for neoplasia in most animals is age. Biological aging increases the risk of neoplasia in many ways, including the accumulation of damage to DNA, proteins, and cells, as well as the loss of mechanisms to prevent and repair this damage. Cancer risk consistently increases with age in dogs and in humans, though individuals who live unusually long may be resistant, leading to lower cancer rates in those of extreme age.^46,47 There are no currently validated therapies specifically for mitigating the increase in cancer risk associated with aging, but this is an active and promising field of research.

Bottom line

Cancer is a common and deadly collection of diseases that diminish the length and quality of life for our animal companions dramatically. Pet owners and veterinarians are highly motivated to seek ways of protecting dogs and cats from these diseases, and the fear of cancer is a common tool for promoting preventive healthcare and marketing products to animal owners. Unfortunately, however, there is no single definitive strategy to prevent cancer.

The risk of developing some specific types of neoplasia can be reduced by targeted strategies; such as neutering to prevent reproductive tract cancers and vaccinating cats against feline leukemia to prevent virus-associated neoplasia.

More general preventative healthcare strategies have been shown to reduce cancer risk in humans, including avoiding obesity, engaging in regular physical activity, and minimizing exposure to cigarette smoke. These likely also reduce cancer risk in dogs and cats as well, though evidence for this is sparse. The future holds the promise of more clearly and broadly effective strategies, such as dietary manipulation and therapies to retard the effect of aging on cancer risk, but there is much research yet to be done to realize this promise. For now, good general husbandry and regular veterinary care remains the most reasonable cancer-prevention approach for most pet owners.

Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists' opinions do not necessarily reflect those of Veterinary Practice News.

References

1. McKenzie BA. Is cancer incidence increasing in dogs and cats? Vet Pract News. October 2018:38-39.
2. Lei J, Ploner A, Elfström KM, et al. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020;383(14):1340-1348. doi:10.1056/NEJMoa1917338.
3. Louwerens M, London CA, Pedersen NC, Lyons LA. Feline lymphoma in the post-feline leukemia virus era. J Vet Intern Med. 2005;19(3):329-335. doi:10.1892/0891-6640(2005)19[329:flitpl]2.0.co;2.
4. Countries I of M (US) C on CC in LM-I, Sloan FA, Gelband H. Cancer Causes and Risk Factors and the Elements of Cancer Control. 2007. https://www.ncbi.nlm.nih.gov/books/NBK54025/. Accessed September 17, 2021.
5. Walser T, Cui X, Yanagawa J, et al. Smoking and lung cancer: the role of inflammation. Proc Am Thorac Soc. 2008;5(8):811-815. doi:10.1513/pats.200809-100TH.
6. Thun MJ, Jemal A. How much of the decrease in cancer death rates in the United States is attributable to reductions in tobacco smoking? Tob Control. 2006;15(5):345-347. doi:10.1136/tc.2006.017749.
7. Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ. 2000;321(7257):323-329. doi:10.1136/bmj.321.7257.323.
8. Moolgavkar SH, Holford TR, Levy DT, et al. Impact of Reduced Tobacco Smoking on Lung Cancer Mortality in the United States During 1975–2000. JNCI J Natl Cancer Inst. 2012;104(7):541-548. doi:10.1093/jnci/djs136.
9. Smith N, Luethcke KR, Craun K, Trepanier L. Risk of bladder cancer and lymphoma in dogs is associated with pollution indices by county of residence. Vet Comp Oncol. September 2021. doi:10.1111/vco.12771.
10. Andrade FH, Figueiroa FC, Bersano PR, Bissacot DZ, Rocha NS. Malignant mammary tumor in female dogs: environmental contaminants. Diagn Pathol. 2010;5(1):45. doi:10.1186/1746-1596-5-45.
11. Gavazza A, Presciuttini S, Barale R, Lubas G, Gugliucci B. Association Between Canine Malignant Lymphoma, Living in Industrial Areas, and Use of Chemicals by Dog Owners. J Vet Intern Med. 2001;15(3):190-195. doi:10.1111/j.1939-1676.2001.tb02310.x.
12. Takashima-Uebelhoer BB, Barber LG, Zagarins SE, et al. Household chemical exposures and the risk of canine malignant lymphoma, a model for human non-Hodgkin's lymphoma. Environ Res. 2012;112:171-176. doi:10.1016/J.ENVRES.2011.12.003.
13. Glickman LT, Domanski LM, Maguire TG, Dubielzig RR, Churg A. Mesothelioma in pet dogs associated with exposure of their owners to asbestos. Environ Res. 1983;32(3):305-313. doi:10.1016/0013-9351(83)90114-7.
14. Bertone ER, Snyder LA, Moore AS. Environmental and Lifestyle Risk Factors for Oral Squamous Cell Carcinoma in Domestic Cats. J Vet Intern Med. 2003;17(4):557-562. doi:10.1111/j.1939-1676.2003.tb02478.x.
15. Bertone ER, Snyder LA, Moore AS. Environmental Tobacco Smoke and Risk of Malignant Lymphoma in Pet Cats. Am J Epidemiol. 2002;156(3):268-273. doi:10.1093/aje/kwf044
16. Zierenberg-Ripoll A, Pollard RE, Stewart SL, et al. Association between environmental factors including second-hand smoke and primary lung cancer in dogs. J Small Anim Pract. 2018;59(6):343-349. doi:10.1111/jsap.12778.
17. Reif JS, Dunn K, Ogilvie GK, Harris CK. Passive Smoking and Canine Lung Cancer Risk. Am J Epidemiol. 1992;135(3):234-239. doi:10.1093/oxfordjournals.aje.a116276.
18. Reif JS, Bruns C, Lower KS. Cancer of the Nasal Cavity and Paranasal Sinuses and Exposure to Environmental Tobacco Smoke in Pet Dogs. Am J Epidemiol. 1998;147(5):488-492. doi:10.1093/oxfordjournals.aje.a009475.
19. Colditz GA, Peterson LL. Obesity and Cancer: Evidence, Impact, and Future Directions. Clin Chem. 2018;64(1):154-162. doi:10.1373/clinchem.2017.277376.
20. Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci. 2012;1271(1):37-43. doi:10.1111/j.1749-6632.2012.06750.x
21. De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes. 2013;2013:291546. doi:10.1155/2013/291546
22. Wienecke A, Neuhauser H, Kraywinkel K, Barnes B. Cancers Potentially Preventable through Excess Weight Reduction in Germany in 2010. Obes Facts. 2018;11(5):400-412. doi:10.1159/000490150.
23. Ma C, Avenell A, Bolland M, et al. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849. doi:10.1136/bmj.j4849.
24. Luo J, Hendryx M, Manson JE, et al. Intentional Weight Loss and Obesity-Related Cancer Risk. JNCI Cancer Spectr. 2019;3(4). doi:10.1093/jncics/pkz054.
25. Lund EM, Armstrong PJ, Kirk CA, Klausner JS. Prevalence and Risk Factors for Obesity in Adult Dogs from Private US Veterinary Practices. Int J Appl Res Vet Med. 2006;4(2):177-186. http://jarvm.com/articles/Vol4Iss2/Lund.pdf. Accessed September 17, 2021.
26. German AJ. The Growing Problem of Obesity in Dogs and Cats. J Nutr. 2006;136(7):1940S-1946S. doi:10.1093/jn/136.7.1940S.
27. Weeth LP. Other Risks/Possible Benefits of Obesity. Vet Clin North Am Small Anim Pract. 2016;46(5):843-853. doi:10.1016/j.cvsm.2016.04.007.
28. Glickman LT, Schofer FS, McKee LJ, Reif JS, Goldschmidt MH. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J Toxicol Environ Health. 1989;28(4):407-414. doi:10.1080/15287398909531360
29. Weeth LP, Fascetti AJ, Kass PH, Suter SE, Santos AM, Delaney SJ. Prevalence of obese dogs in a population of dogs with cancer. Am J Vet Res. 2007;68(4):389-398. doi:10.2460/ajvr.68.4.389.
30. Friedenreich CM, Neilson HK, Lynch BM. State of the epidemiological evidence on physical activity and cancer prevention. Eur J Cancer. 2010;46(14):2593-2604. doi:10.1016/J.EJCA.2010.07.028.
31. Kohler LN, Garcia DO, Harris RB, Oren E, Roe DJ, Jacobs ET. Adherence to Diet and Physical Activity Cancer Prevention Guidelines and Cancer Outcomes: A Systematic Review. Cancer Epidemiol Biomarkers Prev. 2016;25(7):1018-1028. doi:10.1158/1055-9965.EPI-16-0121.
32. Thomson CA, McCullough ML, Wertheim BC, et al. Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative. Cancer Prev Res. 2014;7(1):42-53. doi:10.1158/1940-6207.CAPR-13-0258.
33. Botteri E, de Lange T, Tonstad S, Berstad P. Exploring the effect of a lifestyle intervention on cancer risk: 43-year follow-up of the randomized Oslo diet and antismoking study. J Intern Med. 2018;284(3):282-291. doi:10.1111/joim.12765.
34. Brown JC, Ligibel JA. Lifestyle Interventions for Breast Cancer Prevention. Curr Breast Cancer Rep. 2018;10(3):202-208. doi:10.1007/s12609-018-0281-z.
35. McKenzie BA. Are vegetarian diets good for pets? Vet Pract News. July 2019:26-27.
36. McKenzie BA. Pet Food Myths. Vet Pract News. June 2020:16-18.
37. McKenzie BA. Canned or Dry Food: What's Better for Cats. Vet Pract News. September 2019:22-23.
38. McKenzie BA. Is Keto Kind to Pets? Vet Pract News. January 2020:30-31.
39. McKenzie B. Is banning "artificial" ingredients based on fear or science? Vet Pract News. March 2019:36-37.
40. McKenzie B. Debating Raw Diets. Vet Pract News. January 2019:30-31. https://www.veterinarypracticenews.com/debating-raw-diets-january-2019/.
41. Baretta LT, Dhein JDO, Lupion CG, et al. Occurrence of Cutaneous Neoplasia in Dogs with Actinic Dermatitis in a Veterinary Medical Teaching Hospital - UFRGS, Brazil. Acta Sci Vet. 2021;49(0). doi:10.22456/1679-9216.108639.
42. Scarff D. Solar (actinic) dermatoses in the dog and cat. Companion Anim. 2017;22(4):188-196. doi:10.12968/coan.2017.22.4.188.
43. Couteau C, Bruet V, Bourdeau P, Coiffard L. Détermination in vitro de l'efficacité photo-protectrice et statut juridique des produits proposés pour un usage vétérinaire. Rev Med Vet (Toulouse). 2019;170(1/3):34-37. https://www.cabdirect.org/cabdirect/abstract/20193096839. Accessed September 24, 2021.
44. Kimura T, Doi K. Protective Effects of Sunscreens on Sunburn and Suntan Reactions in Cross-bred Mexican Hairless Dogs. Vet Dermatol. 1994;5(4):175-188. doi:10.1111/j.1365-3164.1994.tb00029.x
45. McKenzie B. Evaluating the benefits and risks of neutering dogs and cats. CAB Rev Perspect Agric Vet Sci Nutr Nat Resour. 2010;5. doi:10.1079/PAVSNNR20105045.
46. Cooley DM, Schlittler DL, Glickman LT, Hayek M, Waters DJ. Exceptional Longevity in Pet Dogs Is Accompanied by Cancer Resistance and Delayed Onset of Major Diseases. Journals Gerontol Ser A Biol Sci Med Sci. 2003;58(12):B1078-B1084. doi:10.1093/gerona/58.12.B1078.
47. Kent MS, Burton JH, Dank G, et al. Association of cancer-related mortality, age and gonadectomy in golden retriever dogs at a veterinary academic center (1989-2016). PLoS One 2018. doi:10.1371/journal.pone.0192578.