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Posted: May 18th, 2016

Epidemiologic Studies of Risk Factors for Cancer in Pet Dogs

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Introduction

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Chapter 1: Epidemiologic Studies of Risk Factors for Cancer in Pet Dogs

1.1 Frequency of Cancer in dogs by Site

1.2 Epidemiology of Cancer of Selected Sites in Dogs

1.2.1 Female Breast Cancer

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1.2.2 Testicular Cancer

References

Introduction

Cancer is one of the most important disease that affects humans but also companion animals. In 2008, 7.6 million cancer deaths were reported in humans while by 2030 [1] this number is expected to be over 13.2 million even though the diagnosis and treatment of cancer have been radically improved.

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Cancer is considered the main cause of death in pet animals [2, 3] and the second cause of death in humans, while its frequency in dogs is two times higher than that of humans [5].

Many types of cancer in companion animals have similar behavior, pathologic expression and risk factors with that of humans due to carcinogens present in the environment such as tobacco smoke, pesticides or other. http://www.petcancerawareness.org/facts.html)

However, it has been very difficult to estimate the morbidity and mortality rate of cancer in animals. In human medicine, cancer cases have been registered with all the epidemiological data and studied since 1940s, whereas in veterinary medicine cancer cases have been recorded in smaller numbers in a non-organized manner and there is very little information nowadays on the occurrence of different types of neoplasms in companion animals. Cancer registries provide information regarding the risk assessment for each case, the evaluation of incidence, epidemiological data, treatment options and the identification of risk factors [6]. Therefore it is very important to keep records of all the epidemiological information.

Chapter 1: Epidemiologic Studies of Risk Factors for Cancer in Pet Dogs

1.1 Frequency of Cancer in dogs by Site

In Alameda and Contra Costa Counties, California a study was conducted from July 1963 to June 1966 [7, 8] in order to identify the frequency of neoplasms of different sites in a population.

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Data were collected from 65 veterinary practices regarding the age, sex, breed and whether the owner was using veterinary services regularly. Biopsy specimens were sent to the laboratory and read by a pathologist.

The most frequent cancers in female and male dogs in the 1960s [7] and in humans at the same period and in early 90s [9] are shown in Tables 1 and 2 [14].

Dogs

(1963-1966)

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Women

(1969-1971)

Women

(1988)

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Cancer

% of total

Cancer

% of total

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Cancer

% of total

Breast

51

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Breast

27

Breast

30

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Connective tissue

9

Colon and rectum

15

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Lung and bronchus

13

Malignant melanoma of skin

8

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Corpus uteri

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Colon and rectum

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Lymphoma

6

Cervix

6

Corpus uteri

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6

Mouth and pharynx

5

Lung

5

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Ovary

4

Biliary passages and liver

2

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Ovary

5

Non-Hodgkin’s lymphoma

4

Bone

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2

Leukemia

3

Melanoma of skin

3

Table 1 Most common types of cancer in female dogs and women

Dogs

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(1963-1966)

Men

(1969-1971)

Men

(1988)

Cancer

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% of total

Cancer

% of total

Cancer

% of total

Connective tissue

17

Lung and bronchus

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21

Prostate

29

Testis

16

Prostate

16

Lung and bronchus

15

Malignant melanoma of skin

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14

Colon and rectum

14

Colon and rectum

10

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Mouth and pharynx

10

Urinary bladder

6

Urinary bladder

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6

Lymphoma

10

Buccal cavity and pharynx

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5

Non-Hodgkin’s lymphoma

5

Bone

4

Stomach

4

Malignant melanoma of skin

4

Stomach and intestines

3

Leukemia

4

Oral cavity and pharynx

3

Table 2 Most common types of cancer in male dogs and men

In female dogs, the most common neoplasms were breast cancer, malignant melanoma and lymphoma, whereas in male dogs the major neoplasms were of connective tissue, testis, malignant melanoma, mouth and pharynx.

According to the results of the study, breast cancer is common in both women and female dogs. However, cancer of uterus and ovary are rare in dogs because most of female dogs are spayed at younger age, avoiding the high risk of developing a cancer in old age. Colon and rectal cancers are rare in dogs probably because of diet, physical activity, faster transit time through the intestine and lower genetic predisposition. Lymphoma is relatively common in both humans and dogs.

1.2 Epidemiology of Cancer of Selected Sites in Dogs

1.2.1 Female Breast Cancer

The most common malignant neoplasm in female dogs is breast cancer [7]. The study performed in Alameda/Contra Costa Counties indicates that 51% of the cases were breast cancer if non melanoma skin cancers are excluded.

Adenocarcinomas represent about 76% of breast cancers in dogs. Also in humans adenocarcinomas predominate. In dogs neoplastic lesions are found more frequently in posterior breasts than in anterior. This can be due to the greater growth rate, weight, lobulation and secretion in posterior breasts [10, 11]. Breast cancer incidence increases sharply with age in dogs. The rate of breast cancer occurrence in purebred dogs is two times higher than in crossbred dogs of same age [8].

The main etiology of female breast cancer in dogs is related to ovarian hormones, therefore spaying has proved to protect against mammary gland cancer [8, 12]. However, only if the dog was spayed when it reaches maturity at an age of 2-2 years, protected the animal against breast cancer. Also, in humans it has been proved that premenopausal oophorectomy protects against breast cancer [13] but at the same time in humans it is unheard of to perform oophorectomy before puberty. So unfortunately, it is practically impossible to apply this information obtained from the studies in dogs. Another study suggests that the development of malignant tumors depends on the overexpression of the oncogene c-erbB-2 [15]. An experimental study proposes that high doses of oral contraceptives can result in mammary gland cancer in beagles [16]. Furthermore, an observational study found that there is a relation between the diet (amount of fat and protein) and the risk for developing breast cancer [17]. This study suggests that a high protein diet in combination with a low fat intake was associated with higher survival rate [18]. Unspayed dogs that were underweight as puppies had half the risk for developing mammary gland cancer compared to unspayed dogs that were not underweight as puppies [14].

1.2.2 Testicular Cancer

The most common types of testicular cancer in dogs are sertoli cell tumors, seminomas and interstitial cell tumors [19]. Incidence rate of testicular cancer in dog increases as the dog gets older, although sertoli cell tumors occur at a younger age compared to the other types of tumors [20].

Several studies have reported that dogs with cryptorchidism have a noticeable higher risk to develop testicular seminoma and sertoli cell tumor [20-23]. In dogs with cryptorchidism, tumors usually develop at a younger age than in other dogs [24]. Also, testicular cancer is more likely to appear in dogs with inguinal hernia [21].

Military working dogs who served in Vietnam had a higher risk for developing seminoma [25]. This is probably due to the fact that these dogs came in contact with several zoonotic and parasitic infections which led to the overuse of certain drugs, such as tetracycline. Also use of chemicals like phenoxy herbicides and malathion could be the cause. It is not known which was the specific exposure that caused the higher incidence of seminomas [26, 27].

References

  1. American Cancer Society (2011). Global Cancer Facts & Figures, 2nd Edition, Atlanta: American Cancer Society
  2. Bonnett B, NA Egenvall, Hedhammar A and Olson P (2005). Mortality in over 350000 insured Swedish dogs from 1995−2000: I. Breed, gender, age and causes specific rates. Acta Vet. Scand. 46: 105−120.
  3. Merlo DF, Rossi L, Pellegrino C, Ceppi M, Cardellino U, Capurro C, Ratto A, Sambucco PL, Sestito V, Tanara G and Bocchini V (2008). Cancer Incidence in Pet Dogs: Findings of the Animal Tumor Registry of Genoa, Italy. J. Vet. Intern. Med. 22: 976 – 984
  4. Siegel R, Naishadham D and Jemal A (2013). Cancer statistics, 2013. CA: A Cancer J. Clin. 63: 11–30.
  5. Rungsipipat A, Sunyasootcharee B, Ousawaphlangchai L, Sailasuta A, Thanawongnuwech R and Teankum K (2003). Neoplasms of dogs in Bangkok. Thailand J. Vet. Med. 33: 59–66
  6. Marta Vascellari, Elisa Baioni, Giuseppe Ru, Antonio Carminato and Franco Mutinelli (2009) Animal tumor registry of two provinces in northern Italy: incidence of spontaneous tumors in dogs and cats, BioMed Central Ltd, ISSN 1746-6148, doi 10.1186/1746-6148-5-39
  7. Dorn CR, Taylor DON, Frye FL, et al. (1968). Survey of animal neoplasms in Alameda and Contra Costa Counties, California. I. Methodology and description of cases. J Natl Cancer Inst. 40:295-305.
  8. Dorn CR, Taylor DON, Schneider R, et al. (1968). Survey of animal neoplasms in Alameda and Contra Costa Counties, California. II. Cancer morbidity in dogs and cats from Alameda County. J Natl Cancer Inst. 40:307-18.
  9. Parker SL, Tong T, Bolden S, et al. (1998) Cancer statistics, CA Cancer J Clin. 48:6-29.
  10. Warner MR (1976), Age, incidence and site distribution of mammary dysplasias in young beagle bitches. J Natl Cancer Inst. 57:57-61.
  11. Else RW, Hannant D. (1979), Some epidemiological aspects of mammary neoplasia in the bitch. Vet Rec. 104:296-304.
  12. Schneider R, Dorn CR, Taylor DON (1969), Factors influencing canine mammary cancer development and post-surgical survival. J Natl Cancer Inst. 43:1249-61.
  13. Feinleib M (1968), Breast cancer and artificial menopause: a cohort study. J Natl Cancer Inst. 41:315-29.
  14. Kelsey J., Moore A. and Glickman L. (1998), Epidemiologic Studies of Risk Factors for Cancer in Pet Dogs, Epidemiology reviews 20(2):204-17
  15. Ahern TE, Bird RC, Bird AEC, et al (1996), Expression of the oncogene c-erbB-2 in canine mammary cancers and tumorderived cell lines. Am J Vet Res. 57:693-6.
  16. Kwapien RP, Giles RC, Geil RG, et al. (1980), Malignant mammary tumors in beagle dogs dosed with investigational oral contraceptive steroids. J Natl Cancer Inst. 65:137-44.
  17. Sonnenschein EG, Glickman LT, Goldschmidt MH, et al. (1991), Body conformation, diet, and risk of breast cancer in pet dogs: a case-control study. Am J Epidemiol. 133:694-703.
  18. Shofer FS, Sonnenschein EG, Goldschmidt MH, et al. (1989), Histopathologic and dietary prognostic factors for canine mammary carcinoma. Breast Cancer Res Treat 13:49-60.
  19. Ogilvie GK, Moore AS. (1995), Managing the veterinary cancer patient. Trenton, NJ: Veterinary Learning Systems
  20. Hayes HM Jr, Pendergrass TW. (1976) Canine testicular tumors: epidemiologic features of 410 dogs. Int J Cancer 18: 482-7.
  21. Hayes HM Jr, Wilson GP, Pendergrass TW, et al. (1985) Canine cryptorchism and subsequent testicular neoplasia: case-control study with epidemiologic update. Teratology; 32:51-6.
  22. Nieto JM, Pizarro M, Balaguer LM, et al. (1989) Canine testicular tumors in descended and cryptorchid testes. DTW Dtsch Tierarztl Wochenschr; 96:186-9.
  23. Reif JS, Brodey RS. (1969) The relationship between cryptorchidism and canine testicular neoplasia. J Am Vet Med Assoc; 155:2005-10.
  24. Reif JS, Maguire TG, Kenney RM, et al. (1979) A cohort study of canine testicular neoplasia. J Am Vet Med Assoc. 175: 719-23.
  25. Hayes HM, Tarone RE, Casey HW, et al. (1990) Excess of seminomas observed in Vietnam service US military working dogs. J Natl Cancer Inst. 82:1042-6.
  26. Tarone RE, Hayes HM, Hoover RN, et al. (1991) Service in Vietnam and risk of testicular cancer. J Natl Cancer Inst. 83: 1497-9.
  27. Bullman TA, Watanabe KK, Kang HK. (1994) Risk of testicular cancer associated with surrogate measures of agent orange exposure among Vietnam veterans in the Agent Orange Registry. Ann Epidemiol. 4:11-16.

14. Warner MR. Age, incidence and site distribution of mammary dysplasias in young beagle bitches. J Natl Cancer Inst 1976; 57:57-61.

15. Else RW, Hannant D. Some epidemiological aspects of mammary neoplasia in the bitch. Vet Rec 1979; 104:296-304.

16. Schneider R, Dorn CR, Taylor DON. Factors influencincanine mammary cancer development and postsurgicavival. J Natl Cancer Inst 1969;43:1249-61.

9. Dorn CR, Taylor DON, Frye FL, et al. Survey of animal neoplasms in Alameda and Contra Costa Counties, California.

I. Methodology and description of cases. J Natl Cancer Inst 1968;40:295-305.

10. Dorn CR, Taylor DON, Schneider R, et al. Survey of animal neoplasms in Alameda and Contra Costa Counties, California.

II. Cancer morbidity in dogs and cats from Alameda County. J Natl Cancer Inst 1968;40:307-18.

12. Parker SL, Tong T, Bolden S, et al. Cancer statistics, 1998. CA Cancer J Clin 1998;48:6-29.

20. Feinleib M. Breast cancer and artificial menopause: a cohort study. J Natl Cancer Inst 1968;41:315-29.

30. Ahern TE, Bird RC, Bird AEC, et al. Expression of the oncogene c-erbB-2 in canine mammary cancers and tumorderived cell lines. Am J Vet Res 1996;57:693-6.

31. Kwapien RP, Giles RC, Geil RG, et al. Malignant mammary tumors in beagle dogs dosed with investigational oral contraceptive steroids. J Natl Cancer Inst 1980,65:137-44.

19. Sonnenschein EG, Glickman LT, Goldschmidt MH, et al. Body conformation, diet, and risk of breast cancer in pet dogs: a case-control study. Am J Epidemiol 1991;133:694-703.

32. Shofer FS, Sonnenschein EG, Goldschmidt MH, et al. Histopathologic and dietary prognostic factors for canine mammary carcinoma. Breast Cancer Res Treat 1989;13:49-60.

13. Ogilvie GK, Moore AS. Managing the veterinary cancer patient. Trenton, NJ: Veterinary Learning Systems, 1995.

33. Hayes HM Jr, Pendergrass TW. Canine testicular tumors: epidemiologic features of 410 dogs. Int J Cancer 1976; 18: 482-7.

34. Hayes HM Jr, Wilson GP, Pendergrass TW, et al. Canine cryptorchism and subsequent testicular neoplasia: case-control study with epidemiologic update. Teratology 1985;32:51-6.

35. Nieto JM, Pizarro M, Balaguer LM, et al. Canine testicular tumors in descended and cryptorchid testes. DTW Dtsch Tierarztl Wochenschr 1989;96:186-9.

36. Reif JS, Brodey RS. The relationship between cryptorchidism and canine testicular neoplasia. J Am Vet Med Assoc 1969; 155:2005-10.

37. Reif JS, Maguire TG, Kenney RM, et al. A cohort study of canine testicular neoplasia. J Am Vet Med Assoc 1979;175: 719-23.

39. Hayes HM, Tarone RE, Casey HW, et al. Excess of seminomas observed in Vietnam service US military working dogs. J Natl Cancer Inst 1990;82:1042-6.

40. Tarone RE, Hayes HM, Hoover RN, et al. Service in Vietnam and risk of testicular cancer. J Natl Cancer Inst 1991 ;83: 1497-9.

41. Bullman TA, Watanabe KK, Kang HK. Risk of testicular cancer associated with surrogate measures of agent orange exposure among Vietnam veterans in the Agent Orange Registry. Ann Epidemiol 1994;4:11-16.

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