The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis
Cancer is a leading cause of death in domestic dogs. Deaths due to cancer vary widely among breeds, providing an opportunity for testing the multi-stage model of carcinogenesis. This model underpins evolutionary and basic studies of cancer suppression and predicts a linear increase in cancer with br...
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| Format: | Article |
| Language: | English |
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The Royal Society
2024-01-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.231356 |
| _version_ | 1797338477286653952 |
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| author | Leonard Nunney |
| author_facet | Leonard Nunney |
| author_sort | Leonard Nunney |
| collection | DOAJ |
| description | Cancer is a leading cause of death in domestic dogs. Deaths due to cancer vary widely among breeds, providing an opportunity for testing the multi-stage model of carcinogenesis. This model underpins evolutionary and basic studies of cancer suppression and predicts a linear increase in cancer with breed size, an expectation complicated by bigger breeds having a shorter lifespan (decreasing risk). Using three independent datasets, the weight and lifespan of breeds provided a good fit of lifetime cancer mortality to the multi-stage model, the fit suggesting many canine cancers are initiated by four driver mutations. Of 85 breeds in more than one dataset, only flat-coated retriever showed significantly elevated cancer mortality, with Scottish terrier, Bernese mountain dog and bullmastiff also showing notable risk (greater than 50% over expected). Analysis of breed clades suggested terriers experience elevated cancer mortality. There was no evidence that the lower mass-specific metabolic rate of larger breeds reduced cancer risk. Residuals indicated increased breed inbreeding shortened expected lifespan, but had no overall effect on cancer mortality. The results provide a baseline for identifying increased breed risk for specific cancers and demonstrate that, unless selection promotes increased cancer suppression, the evolution of larger longer-lived animals leads to a predictable increased cancer risk. |
| first_indexed | 2024-03-08T09:31:47Z |
| format | Article |
| id | doaj.art-521ecebe6db44df4a6ee7bbd83bb39c9 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-03-08T09:31:47Z |
| publishDate | 2024-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-521ecebe6db44df4a6ee7bbd83bb39c92024-01-31T00:05:54ZengThe Royal SocietyRoyal Society Open Science2054-57032024-01-0111110.1098/rsos.231356The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesisLeonard Nunney0Department of Evolution, Ecology, and Organismal Biology, University of California Riverside, 900 University Avenue, Riverside, CA 92521, USACancer is a leading cause of death in domestic dogs. Deaths due to cancer vary widely among breeds, providing an opportunity for testing the multi-stage model of carcinogenesis. This model underpins evolutionary and basic studies of cancer suppression and predicts a linear increase in cancer with breed size, an expectation complicated by bigger breeds having a shorter lifespan (decreasing risk). Using three independent datasets, the weight and lifespan of breeds provided a good fit of lifetime cancer mortality to the multi-stage model, the fit suggesting many canine cancers are initiated by four driver mutations. Of 85 breeds in more than one dataset, only flat-coated retriever showed significantly elevated cancer mortality, with Scottish terrier, Bernese mountain dog and bullmastiff also showing notable risk (greater than 50% over expected). Analysis of breed clades suggested terriers experience elevated cancer mortality. There was no evidence that the lower mass-specific metabolic rate of larger breeds reduced cancer risk. Residuals indicated increased breed inbreeding shortened expected lifespan, but had no overall effect on cancer mortality. The results provide a baseline for identifying increased breed risk for specific cancers and demonstrate that, unless selection promotes increased cancer suppression, the evolution of larger longer-lived animals leads to a predictable increased cancer risk.https://royalsocietypublishing.org/doi/10.1098/rsos.231356cancermulti-stage modeldog breedsinbreedinglifespanmetabolic rate |
| spellingShingle | Leonard Nunney The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis Royal Society Open Science cancer multi-stage model dog breeds inbreeding lifespan metabolic rate |
| title | The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis |
| title_full | The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis |
| title_fullStr | The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis |
| title_full_unstemmed | The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis |
| title_short | The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis |
| title_sort | effect of body size and inbreeding on cancer mortality in breeds of the domestic dog a test of the multi stage model of carcinogenesis |
| topic | cancer multi-stage model dog breeds inbreeding lifespan metabolic rate |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.231356 |
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