Estimating canine cancer incidence: findings from a population-based tumour registry in northwestern Italy

Canine cancer registry data can be put to good use in epidemiological studies. Quantitative comparison of tumour types may reveal unusual cancer frequencies, providing direction for research and generation of hypotheses of cancer causation in a specific area, and suggest leads for identifying risk factors.

The pivotal role of the sentinel animal some species play at a low level in the trophic chain, e.g., to show the effect of endocrine disruptors, [1] could also be assumed by dogs. The existence of a tumour registry in this species can pinpoint variations in cancer incidence in target organs. One task of such registries is to determine whether potential correlations exist between an increase or decrease in cancer incidence and environmental hazards. In a study conducted 25 years ago on companion animals as a sentinel for environmentally related human diseases, a correlation was found whereby changes in the canine proportionate incidence ratios preceded human incidence rates by 2 years, suggesting that fluctuations in proportionate incidence ratios of tumours in dogs may be useful for predicting changes in cancer patterns in humans [2]. Because these variations can only be discerned when the size of an observed population is known, and knowledge of the animal population size of a specific area is required for estimating the incidence of zoonotic diseases [3], veterinary epidemiologists face numerous hurdles to arriving at a correct estimate of an animal population at risk.

To get around this problem, some registries have obtained the denominator from pet insurance company databases [4, 5], but with the risk of having an incomplete denominator and introducing a systematic error. Insured dogs likely represent a selected subset of the real composition of an area’s dog population. [6]. Recognizing this limitation, veterinary studies have underscored the importance of selecting a delimited geographic area as referential for case collection when establishing animal population-based tumour registries. After an area has been selected, a distinction is made between cases belonging to the area and those not belonging to it. Cases belonging to the area but diagnosed outside of it then need to be identified and retrieved, and cases of animals living outside of it need to be excluded. It is acknowledged that the owners of dogs with cancer will often use veterinary services whereby cases are detected and reported, ultimately restricting the denominator to dogs receiving veterinary care.

The first population-based canine tumour registry was set up by the California State Department of Public Health to estimate the cancer incidence in dogs and cats resident in two counties in California, and to measure the effects of age, sex and breed on cancer development [7]. Over a 3-year period, malignant neoplasm cases in dogs and cats were reported to the registry through the collaboration of county veterinarians. The cases were categorized by their primary tumour site according to the International Classification of Diseases, Revision 7 (ICD-7). The estimated annual incidence rates for malignant cancers of all anatomic sites were 381.2/100,000 dogs and 155.8/100,000 cats.

Ten years later, MacVean et al. [8] investigated the denominator for the cancer incidence rate for dogs seen by veterinarians in one year in two counties. Histopathological diagnosis was offered free to the practitioners participating in the registry. The annual incidence rate for malignant neoplasms was 507/100,000 dogs, or double that of the Californian registry. Other European studies, using as denominator the cynological organization databases, reported incidence rates for some specific breeds [9–11].

The results of two cancer registration projects in Italy have recently been published. The Animal Tumour Registry of Genoa estimated an incidence rate for malignant cancers of 185.7/100,000 dogs [12]. The Animal Tumour Registry of Venice and Vicenza counties was set up in 2005 and provides free histopathological testing to veterinary practices in its catchment area. The estimated incidence rate for malignant neoplasms was 142.8/100,000 dogs [13].

Here we report canine cancer incidence data collected between 2001 and 2008 for a small, well-delimited geographical area in northwestern Italy. As the data were obtained from a population-based registry, the Piedmont Canine Cancer Registry, for an area without any known specific environmental hazard, they may be considered a reliable estimate of reference incidence rates and so may serve as comparison data for other registries.

Here we present the findings obtained from a canine population-based cancer registry that we conducted in northwestern Italy for a 90-month period from 2001 to 2008. The Piedmont canine cancer registry is one of few of its kind whose operations have been consistently supported by long-term public funding. The incidence rate of malignant and benign tumours was about 800 and 900 cases per 100,000 dog-years at risk, respectively, with the largest impact on females and purebred dogs. The highest incidence rates by sex and tumour site were observed for mammary and cutaneous tissues in females and cutaneous tissues and testicles in males. These results were obtained by paying particular attention to the validity of the data collection process, thus minimizing the potential for bias.

Given the constraints derived from working with a canine population, considerable effort was expended to estimate the relevant denominators in terms of population size and structure. Moreover, we were able to obtain detailed reports of cases of incidental tumours by selecting a small-medium size catchment area and through public awareness campaigns coupled with enhanced participation of veterinary practices offered scientific support and histological examinations free of charge.

Though our study may have limitations, they do not necessarily compromise its internal or external validity. By mobilizing the available human and economic resources and restricting the cancer registration to a relatively small area (canine population of about 10,000 units), we were able to maintain the activities for a 90-month period, with a total of about 70,000 dog-years at risk which were then used as the overall denominator. The resulting overall incidence rates were found to be stable; however, less precise estimates could also have been obtained by looking at subgroups (e.g., municipality, breed, age class). For this reason, we carried out few subgroups analyses within our dataset.

As mentioned, there remains the potential for some residual bias in the quantification of the denominators and the numerators. Selection bias is less likely to be a problem with population-based registries than, for example, hospital-based registries [18, 19] or canine registries using databases from pet insurance companies where cross-breed dogs or aged dogs are apt to be underrepresented [6, 20].

With regard to the capture-recapture strategy that was applied to estimate the unknown canine population size, some of the assumptions this approach [14] requires may not have been fully met, e.g., working on a closed population and using random samples (assumptions that are unlikely to be met in a field situation); however, there are no evident reasons that preclude that the recruited dogs were equally likely to be captured in each of the two samples. The midterm census of 44 of the 46 municipalities in the catchment area indicated no large deviation from the direct enumeration of the existent dogs.

Additionally the population structure by breed- or age-strata may not be as precise as the population size. The structure was obtained from our second capture (the anonymous questionnaire survey) only. Unfortunately, the data on the first capture (i.e., the canine identification and registration system) and the midterm census were available only in hard copy format, precluding any practical way to further analyse the data. Therefore, the incidence rates are likely to be more robust when the denominator was the entire population (e.g., crude malignant rate or site-specific rates) rather than when the denominators referred to individual breeds or age classes.

Finally, with regard to the cases of incidental tumours, a certain degree of underdetection may have occurred. In particular, a proportion of tumours may have gone undiagnosed (e.g., a deep organ tumour), or not reported as not requiring histological confirmation (e.g., osteosarcoma, lymphoma) or may have been diagnosed by laboratories other than ours and not reported by the collaborating veterinary practitioners. In an attempt to minimize these problems, the collaborating veterinary practitioners were given standardized case report forms and local laboratories were contacted.

Assuming an unbiased estimation of cancer occurrence, the incidence rates in our registry are higher than those reported by similar population-based registries in Italy [12, 13] where the crude incidence rates for all malignant cancer were less than 200 cases per 100,000 dog-years at risk. The differences, albeit evident, are smaller when the comparison is carried out with data from international population-based registries ([7, 8, 21]). Rates higher than ours were reported in a registry that used as a denominator for cancer incidence all dogs insured with a pet U.K. insurance company [4]. The higher cancer rates we found cannot be convincingly linked to exposure of the dogs to as yet undetected environmental risk factors in the catchment area. Instead, the excess incidence may more likely stem from the effect of a different distribution of confounding factors such as age and breed, which are known determinants of cancer in dogs [22–24]. Unfortunately, in most of the comparable studies, data on the population structure by age and breed were not available, preventing any appropriate comparison of rates. Moreover unlike other studies, in ours the denominators were reduced to take into account the real proportion of dogs under veterinary care, an adjustment not reported elsewhere.

Another explanation for the high cancer rates we found may be due to the way we managed the data on multiple primary tumours, which are a common finding in dogs [25–27]. Based on the histopathological diagnosis, each type of neoplasm was classified as a separate cancer and added to the numerator. Other canine registries may not have done this. Finally, the potential risk of overestimation due to the inclusion of cases sourced from outside the registry catchment area was minimized by applying the preliminary case inclusion/exclusion criteria established in the registration protocol.

The distribution of cancer types in our registry is fairly consistent with the literature. As reported elsewhere [7–13, 21], the most prevalent malignant neoplasms were mammary carcinoma and cutaneous mastocytoma. The high prevalence of seminoma found in the Norwegian dog population [22] is analogous to the high incidence estimated in our registry. With regard to breed, the higher incidence rates in purebred rather than in cross-breed dogs were evident for Yorkshire terrier and Boxer, breeds known [5, 7, 27] to be particularly at risk of developing neoplasms, for which a genetic predisposition has been suggested. In the female dogs, the observed cancer trend by age matches those seen in other studies, with an exponential increase in elderly females for all tumours [9] or specifically for mammary tumours [5].

Comparison with the recent findings from two other Italian cancer registries [12, 13] shows that the distribution of tumours is substantially similar. In our registry, the ratio of malignant to benign tumours was 0.90:1, as compared to 0.96:1 in Genoa and 1:1 in the Veneto Region. The incidence of malignant cancer was higher in females than in males (2.5 times, 2.7 times, and 1.7 times in the study area, Genoa, and Veneto, respectively) and in purebred dogs than in cross-breed dogs (1.5 times in Piedmont and 2 times in Veneto where data were available). Finally, the distribution by tumour site (mammary and cutaneous/soft tissues tumours in females and cutaneous/soft tissues and genital tract tumours in males) was quite similar for all three registries. The exceptionally higher incidence of lymphoma in dogs of both sexes in the Genoa registry may have been due to the inclusion of cancers diagnosed by cytology or because of exposure to unknown risk factors present in a large city.

The Piedmont canine cancer registry is based on a large target population that combine rural and urban environments and on a population-based study design; for this reason our findings have the necessary external validity to be generalized, after adjustment for breed and age, to the canine population of northwestern Italy.

Assuming that the incidence rates from a population-based registry have external validity, national and international standards should be developed and shared to be able to make any meaningful comparison across studies. The adoption of an international classification and coding system, like the International Classification of Diseases for Oncology used in human cancer registries [28], would facilitate the exchange of comparable data and the possibility to carry out multicenter studies [29].

Finally, basic epidemiological methods (e.g., standardization techniques) to account for the confounding effect of age and breed should always be applied: data on population structure should be collected and made available in each study and, as proposed by Thrusfield [30], an international normal dog population should be established and shared as an external standard.

As highlighted by Kelsey et al. [19], the data from population-based canine cancer registries may facilitate the identification of a less select group of cases for case-control studies and allow examination of trends over time and geographic differences in cancer incidence. The findings from the current study provide data on the incidence of canine tumours. The incidence rates may be useful for assessing the impact of neoplastic diseases in the canine population in northwestern Italy and may serve as a reference when setting up studies to detect excess risks in the incidence of malignant tumours in dogs used as sentinels for community exposure to environmental carcinogens.