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Cancer in wildlife: patterns of emergence

An Author Correction to this article was published on 31 January 2019

This article has been updated

Abstract

Cancer is ubiquitous in wildlife, affecting animals from bivalves to pachyderms and cetaceans. Reports of increasing frequency demonstrate that neoplasia is associated with substantial mortality in wildlife species. Anthropogenic activities and global weather changes are shaping new geographical limitations for many species, and alterations in living niches are associated with visible examples of genetic bottlenecks, toxin exposures, oncogenic pathogens, stress and immunosuppression, which can all contribute to cancers in wild species. Nations that devote resources to monitoring the health of wildlife often do so for human-centric reasons, including for the prediction of the potential for zoonotic disease, shared contaminants, chemicals and medications, and for observing the effect of exposure from crowding and loss of habitat. Given the increasing human footprint on land and in the sea, wildlife conservation should also become a more important motivating factor. Greater attention to the patterns of the emergence of wildlife cancer is imperative because growing numbers of species are existing at the interface between humans and the environment, making wildlife sentinels for both animal and human health. Therefore, monitoring wildlife cancers could offer interesting and novel insights into potentially unique non-age-related mechanisms of carcinogenesis across species.

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Fig. 1: Oncogenic pressures at the human–animal interface using suburbia as an example.
Fig. 2: Raccoon polyomavirus-induced cellular transformation.
Fig. 3: Toxin-mediated oncogenesis.
Fig. 4: Reproductive system cancers in wildlife.

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Change history

  • 31 January 2019

    In the originally published article, the aetiology of the single case of B cell lymphoma found in the Mountain gorilla was incorrectly referred to as Gibbon lymphocryptovirus 1 in Table 1. The correct aetiology is Gbb lymphocryptovirus 1. This has now been corrected in both the html and PDF versions of the article.

References

  1. Møller, A. P., Erritzøe, J. & Soler, J. J. Life history, immunity, Peto’s paradox and tumours in birds. J. Evol. Biol. 30, 960–967 (2017).

    PubMed  Google Scholar 

  2. Ewald, P. W. & Swain Ewald, H. A. Infection and cancer in multicellular organisms. Phil. Trans. R. Soc. B 370, 20140224 (2015). This paper reviews the diversity of known pathogen-derived neoplasms among all types of multicellular organisms and also addresses the challenges in recognizing cancer in nature.

    PubMed  Google Scholar 

  3. McAloose, D. & Newton, A. L. Wildlife cancer: a conservation perspective. Nat. Rev. Cancer 9, 517–526 (2009). This Review highlights how wildlife cancer is an important threat to some species and establishes tumours in wildlife as sentinels of host changes and the ecosystem.

    CAS  PubMed  Google Scholar 

  4. Rous, P. A transmissible avian neoplasm (Sarcoma of the common fowl). J. Exp. Med. 12, 696–705 (1910).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Fredricks, D. N. & Relman, D. A. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin. Microbiol. Rev. 9, 18–33 (1996).

    CAS  PubMed  Google Scholar 

  6. Pagano, J. S. et al. Infectious agents and cancer: criteria for a causal relation. Semin. Cancer Biol. 14, 453–471 (2004).

    CAS  PubMed  Google Scholar 

  7. zur Hausen, H. Papillomaviruses in the causation of human cancers — a brief historical account. Virology 384, 260–265 (2009).

    CAS  PubMed  Google Scholar 

  8. Lempp, C. et al. Pathological findings in the red fox (Vulpes vulpes), stone marten (Martes foina) and raccoon dog (Nyctereutes procyonoides), with special emphasis on infectious and zoonotic agents in Northern Germany. PLoS ONE 12, e0175469 (2017).

    PubMed  PubMed Central  Google Scholar 

  9. Balkwill, F. & Mantovani, A. Inflammation and cancer: back to Virchow? Lancet 357, 539–545 (2001).

    CAS  PubMed  Google Scholar 

  10. Gobert, A. P. & Wilson, K. T. Human and Helicobacter pylori interactions determine the outcome of gastric diseases. Curr. Top. Microbiol. Immunol. 400, 27–52 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Gagnaire, A., Nadel, B., Raoult, D., Neefjes, J. & Gorvel, J. P. Collateral damage: insights into bacterial mechanisms that predispose host cells to cancer. Nat. Rev. Microbiol. 15, 109–128 (2017).

    CAS  PubMed  Google Scholar 

  12. Sibony, M. & Jones, N. L. Recent advances in Helicobacter pylori pathogenesis. Curr. Opin. Gastroenterol. 28, 30–35 (2012).

    PubMed  Google Scholar 

  13. Bridgeford, E. C. et al. Gastric Helicobacter species as a cause of feline gastric lymphoma: a viable hypothesis. Vet. Immunol. Immunopathol. 123, 106–113 (2008).

    PubMed  PubMed Central  Google Scholar 

  14. Vickers, T. W. et al. Pathology and epidemiology of ceruminous gland tumors among endangered Santa Catalina Island foxes (Urocyon littoralis catalinae) in the Channel Islands, USA. PLoS ONE 10, 1–18 (2015).

    Google Scholar 

  15. Moriarty, M. E. et al. Ear mite removal in the Santa Catalina Island fox (Urocyon littoralis catalinae): controlling risk factors for cancer development. PLoS ONE 10, 1–15 (2015).

    Google Scholar 

  16. Himmel, L. & Cianciolo, R. Nodular typhlocolitis, heterakiasis, and mesenchymal neoplasia in a ring-necked pheasant (Phasianus colchicus) with immunohistochemical characterization of visceral metastases. J. Vet. Diagn. Invest. 29, 561–565 (2017).

    PubMed  Google Scholar 

  17. Hahn, W. C. et al. Creation of human tumour cells with defined genetic elements. Nature 400, 464–468 (1999).

    Article  CAS  Google Scholar 

  18. Acevedo-Whitehouse, K., Gulland, F. M., Greig, D. J. & Amos, W. Inbreeding: disease susceptibility in California sea lions. Nature 422, 35 (2003).

    CAS  Google Scholar 

  19. Buck, C. B. et al. The ancient evolutionary history of polyomaviruses. PLoS Pathol. 12, e1005574 (2016).

    Google Scholar 

  20. DeCaprio, J. A. & Garcea, R. L. A cornucopia of human polyomaviruses. Nat. Rev. Microbiol. 11, 264–276 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Knowles, W. A. in Polyomaviruses and Human Diseases. (ed. Ahsan, N.) 1–25 (Springer-Verlag, New York, 2005).

    Google Scholar 

  22. Feng, H., Shuda, M., Chang, Y. & Moore, P. S. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319, 1096–1100 (2008). This paper uses a focused subtractive viral discovery scheme to find an integrated causative virus in the case of Merkel cell carcinoma of humans. The basis for the search was an association of the cancer with immunosuppression, which underscores the importance of host immunity in the case of viral-associated oncogenesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Starrett, G. J. et al. Merkel cell polyomavirus exhibits dominant control of the tumor genome and transcriptome in virus-associated Merkel cell carcinoma. mBio 8, e02079 (2017). This paper shows how oncogenic proteins of viruses, in this case the T Ag of PyVs, are powerful substitutes for the numerous genetic mutations that usually precede transformation in non-virus-associated cancers.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Dela Cruz, F. N. J. et al. Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States. Emerg. Infect. Dis. 19, 77–84 (2013).

    Google Scholar 

  25. Brostoff, T., Dela Cruz, F. N. J., Church, M. E., Woolard, K. D. & Pesavento, P. A. The raccoon polyomavirus genome and tumor antigen transcription are stable and abundant in neuroglial tumors. J. Virol. 88, 12816–12824 (2014). The data presented in this paper fulfil some of the criteria for viral causality in a wildlife cancer. The stability of the virus as an episome is considered a different oncogenic mechanism than that of the other known PyV associated with cancer (MCPyV).

    PubMed  PubMed Central  Google Scholar 

  26. Stewart, S. E., Eddy, B. E., Gochenour, A. M., Borgese, N. G. & Grubbs, G. E. The induction of neoplasms with a substance released from mouse tumors by tissue culture. Virology 3, 380–400 (1957).

    CAS  PubMed  Google Scholar 

  27. Gross, L. A filterable agent, recovered from Ak leukemic extracts, causing salivary gland carcinomas in C3H mice. Proc. Soc. Exp. Biol. Med. 83, 414–421 (1953).

    CAS  PubMed  Google Scholar 

  28. Cheng, J., DeCaprio, J. A., Fluck, M. M. & Schaffhausen, B. S. Cellular transformation by simian virus 40 and murine polyoma virus T antigens. Semin. Cancer Biol. 19, 218–228 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Church, M. E. et al. Exposure to raccoon polyomavirus (RacPyV) in free-ranging North American raccoons (Procyon lotor). Virology 489, 292–299 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Church, M. E. et al. BRD4 is associated with raccoon polyomavirus genome and mediates viral gene transcription and maintenance of a stem cell state in neuroglial tumour cells. J. Gen. Virol. 97, 2939–2948 (2016).

    CAS  PubMed  Google Scholar 

  31. Colegrove, K. M. et al. Polyomavirus infection in a free-ranging California sea lion (Zalophus californianus) with intestinal T cell lymphoma. J. Vet. Diagn. Invest. 22, 628–632 (2010).

    PubMed  Google Scholar 

  32. Wellehan, J. F. J. et al. Characterization of California sea lion polyomavirus 1: expansion of the known host range of the Polyomaviridae to Carnivora. Infect. Genet. Evol. 11, 987–996 (2011).

    PubMed  Google Scholar 

  33. Leendertz, F. H. et al. African great apes are naturally infected with polyomaviruses closely related to Merkel cell polyomavirus. J. Virol. 85, 916–924 (2011).

    CAS  PubMed  Google Scholar 

  34. Hill, S. C. et al. Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae. J. Gen. Virol. 96, 1411–1422 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Varsani, A. et al. Identification of a polyomavirus in Weddell seal (Leptonychotes weddellii) from the Ross Sea (Antarctica). Arch. Virol. 162, 1403–1407 (2017).

    CAS  PubMed  Google Scholar 

  36. Siqueira, J. D. et al. Endemic infection of stranded southern sea otters (Enhydra lutris nereis) with novel parvovirus, polyomavirus, and adenovirus. J. Wildl. Dis. 53, 532–542 (2017).

    CAS  PubMed  Google Scholar 

  37. Nainys, J., Timinskas, A., Schneider, J., Ulrich, R. G. & Gedvilaite, A. Identification of two novel members of the tentative genus Wukipolyomavirus in wild rodents. PLoS ONE 10, e0140916 (2015).

    PubMed  PubMed Central  Google Scholar 

  38. Kobayashi, S. et al. Detection of novel polyomaviruses in fruit bats in Indonesia. Arch. Virol. 160, 1075–1082 (2015).

    CAS  PubMed  Google Scholar 

  39. Cantalupo, P. G., Buck, C. B. & Pipas, J. M. Complete genome sequence of a polyomavirus recovered from a pomona leaf-nosed bat (Hipposideros pomona) metagenome data set. Genome Announc. 5, e01053-16 (2017).

    PubMed  PubMed Central  Google Scholar 

  40. Varsani, A. et al. A novel papillomavirus in Adélie penguin (Pygoscelis adeliae) faeces sampled at the Cape Crozier colony. Antarctica. J. Gen. Virol. 95, 1352–1365 (2014).

    CAS  PubMed  Google Scholar 

  41. Peretti, A., FitzGerald, P. C., Bliskovsky, V., Pastrana, D. V. & Buck, C. B. Genome sequence of a fish-associated polyomavirus, Black Sea Bass (Centropristis striata) polyomavirus 1. Genome Announc. 3, e01476-14 (2015).

    PubMed  PubMed Central  Google Scholar 

  42. Woolford, L. et al. A novel virus detected in papillomas and carcinomas of the endangered western barred bandicoot (Perameles bougainville) exhibits genomic features of both the Papillomaviridae and Polyomaviridae. J. Virol. 81, 13280–13289 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Woolford, L. et al. Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville). Vet. Pathol. 45, 95–103 (2008).

    CAS  PubMed  Google Scholar 

  44. van Dyk, E. et al. Detection of bovine papillomavirus DNA in sarcoid-affected and healthy free-roaming zebra (Equus zebra) populations in South Africa. J. Virol. Methods 158, 141–151 (2009).

    PubMed  Google Scholar 

  45. Lindsey, C. L. et al. Bovine papillomavirus DNA in milk, blood, urine, semen, and spermatozoa of bovine papillomavirus-infected animals. Gen. Mol. Res. 8, 310–318 (2009).

    CAS  Google Scholar 

  46. Rector, A. & Van Ranst, M. Animal papillomaviruses. Virology 445, 213–223 (2013).

    CAS  PubMed  Google Scholar 

  47. Gaynor, A. M., Fish, S., Duerr, R. S., Cruz, F. N. J. & Pesavento, P. A. Identification of a novel papillomavirus in a Northern Fulmar (Fulmarus glacialis) with viral production in cartilage. Vet. Pathol. 52, 553–561 (2015).

    CAS  PubMed  Google Scholar 

  48. Moore, P. S. & Chang, Y. The conundrum of causality in tumor virology: the cases of KSHV and MCV. Semin. Cancer Biol. 26, 4–12 (2014).

    CAS  PubMed  Google Scholar 

  49. Gulland, F. M., Trupkiewicz, J. G., Spraker, T. R. & Lowenstine, L. J. Metastatic carcinoma of probable transitional cell origin in 66 free-living California sea lions (Zalophus californianus), 1979 to 1994. J. Wildl. Dis. 32, 250–258 (1996).

    CAS  PubMed  Google Scholar 

  50. Lipscomb, T. P. et al. Common metastatic carcinoma of California sea lions (Zalophus californianus): evidence of genital origin and association with novel gammaherpesvirus. Vet. Pathol. 37, 609–617 (2000).

    CAS  PubMed  Google Scholar 

  51. King, D. P. et al. Otarine herpesvirus-1: a novel gammaherpesvirus associated with urogenital carcinoma in California sea lions (Zalophus californianus). Vet. Microbiol. 86, 131–137 (2002).

    CAS  PubMed  Google Scholar 

  52. Buckles, E. L. et al. Otarine Herpesvirus-1, not papillomavirus, is associated with endemic tumours in California sea lions (Zalophus californianus). J. Comp. Pathol. 135, 183–189 (2006).

    CAS  PubMed  Google Scholar 

  53. Dagleish, M. P. et al. The first report of otarine herpesvirus-1-associated urogenital carcinoma in a South American fur seal (Arctocephalus australis). J. Comp. Pathol. 149, 119–125 (2013).

    CAS  PubMed  Google Scholar 

  54. Buckles, E. L. et al. Age-prevalence of Otarine Herpesvirus-1, a tumor-associated virus, and possibility of its sexual transmission in California sea lions. Vet. Microbiol. 120, 1–8 (2007).

    PubMed  Google Scholar 

  55. Browning, H. M., Gulland, F. M., Hammond, J. A., Colegrove, K. M. & Hall, A. J. Common cancer in a wild animal: the California sea lion (Zalophus californianus) as an emerging model for carcinogenesis. Philos. Trans. R Soc. Lond. B Biol. Sci. 370, 1673 (2015). This study highlights how urogenital carcinomas in the California sea lion provide a remarkable model of the complex interaction of environment, pathogens and genetics that are likely involved in most wildlife cancers and that are among the most studied.

    Google Scholar 

  56. Browning, H. M. et al. Evidence for a genetic basis of urogenital carcinoma in the wild California sea lion. Proc. Biol. Sci. 281, 20140240 (2014).

    PubMed  PubMed Central  Google Scholar 

  57. Curry, S. S. et al. Persistent infectivity of a disease-associated herpesvirus in green turtles after exposure to seawater. J. Wildl. Dis. 36, 792–797 (2000).

    CAS  PubMed  Google Scholar 

  58. Ene, A. et al. Distribution of chelonid fibropapillomatosis-associated herpesvirus variants in Florida: molecular genetic evidence for infection of turtles following recruitment to neritic developmental habitats. J. Wildl. Dis. 41, 489–497 (2005).

    CAS  PubMed  Google Scholar 

  59. Herbst, L. H. et al. Experimental transmission of Green turtle fibropapillomatosis using cell-free tumor extracts. Dis. Aquat. Organ. 22, 1–12 (1995).

    Google Scholar 

  60. Foley, A. M., Schroeder, B. A., Redlow, A. E., Fick-Child, K. J. & Teas, W. G. Fibropapillomatosis in stranded green turtles (Chelonia mydas) from the eastern United States (1980–1998): trends and associations with environmental factors. J. Wildl. Dis. 41, 29–41 (2005).

    PubMed  Google Scholar 

  61. Van Houtan, K. S., Hargrove, S. K. & Balazs, G. H. Land use, macroalgae, and a tumor-forming disease in marine turtles. PLoS ONE 5, 1–9 (2010).

    Google Scholar 

  62. dos Santos, R. G. et al. Relationship between fibropapillomatosis and environmental quality: a case study with Chelonia mydas off Brazil. Dis. Aquat. Organ. 89, 87–95 (2010).

    PubMed  Google Scholar 

  63. Greenblatt, R. J. et al. The Ozobranchus leech is a candidate mechanical vector for the fibropapilloma-associated turtle herpesvirus found latently infecting skin tumors on Hawaiian green turtles (Chelonia mydas). J. Virol. 321, 101–110 (2004).

    CAS  Google Scholar 

  64. Smiley Evans, T. et al. Mountain gorilla lymphocryptovirus has Epstein-Barr virus-like epidemiology and pathology in infants. Sci. Rep. 7, 5352 (2017).

    PubMed  PubMed Central  Google Scholar 

  65. Gilardi, K., Whittier, C. & Cranfield, M. in 60th Annual International Conference of the Wildlife Disease Association (Quebec City, Quebec, Canada, 2011).

  66. Hayward, A., Cornwallis, C. K. & Jern, P. Pan-vertebrate comparative genomics unmasks retrovirus macroevolution. Proc. Natl Acad. Sci. USA 112, 464–469 (2015).

    CAS  PubMed  Google Scholar 

  67. Kassiotis, G. Endogenous retroviruses and the development of cancer. J. Immunol. 92, 1343–1349 (2014).

    Google Scholar 

  68. Youssef, G., Wallace, W. A., Dagleish, M. P., Cousens, C. & Griffiths, D. J. Ovine pulmonary adenocarcinoma: a large animal model for human lung cancer. ILAR J. 56, 99–115 (2015).

    CAS  PubMed  Google Scholar 

  69. Fox, K. A. et al. Experimental transmission of bighorn sheep sinus tumors to bighorn sheep (Ovis canadensis canadensis) and domestic sheep. Vet. Pathol. 53, 1164–1171 (2016).

    CAS  PubMed  Google Scholar 

  70. Fox, K. A. et al. Paranasal sinus masses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Vet. Pathol. 48, 706–712 (2011).

    CAS  PubMed  Google Scholar 

  71. Kinney, M. E. & Pye, G. W. Koala retroviruses: a review. J. Zoo Wildl. Med. 47, 387–396 (2016).

    PubMed  Google Scholar 

  72. Xu, W. et al. An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo. Proc. Natl Acad. Sci. USA 110, 11547–11552 (2013).

    CAS  PubMed  Google Scholar 

  73. Shojima, T. et al. Identification of a novel subgroup of koala retrovirus from koalas in Japanese zoos. J. Virol. 87, 9943–9948 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Xu, W. & Eiden, M. Koala retroviruses: evolution and disease dynamics. Ann. Rev. Virol. 2, 119–134 (2015). This paper reveals how koala retroviruses are likely in a unique transient state, as they are presently evolving into endogenous retroviruses, providing an opportunity to study this phenomenon.

    CAS  Google Scholar 

  75. Coffee, L. L., Casey, J. W. & Bowser, P. R. Pathology of tumors in fish associated with retroviruses: a review. Vet. Pathol. 50, 390–403 (2013).

    CAS  PubMed  Google Scholar 

  76. Rovnak, J. & Quackenbush, S. L. Walleye dermal sarcoma virus: molecular biology and oncogenesis. Viruses 2, 1984–1999 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. LaPierre, L. A., Casey, J. W. & Holzschu, D. L. Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D homologs. J. Virol. 72, 8765–8767 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Martineau, D., Bowser, P. R., Wooster, G. A. & Armstrong, L. D. Experimental transmission of a dermal sarcoma in fingerling walleyes (Stizostedion vitreum vitreum). Vet. Pathol. 27, 230–234 (1990).

    CAS  PubMed  Google Scholar 

  79. Bowser, P. R. et al. Swimbladder leiomyosarcoma in Atlantic salmon (Salmo salar) in North America. J. Wildl. Dis. 48, 795–798 (2012).

    PubMed  Google Scholar 

  80. Abram, Q. H., Dixon, B. & Katzenback, B. A. Impacts of low temperature on the teleost immune system. Biology 22, 4 (2017).

    Google Scholar 

  81. Petrie, B., Barden, R. & Kasprzyk-Hordern, B. A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring. Water Res. 72, 3–27 (2015).

    CAS  PubMed  Google Scholar 

  82. Wilkinson, J., Hooda, P. S., Barker, J., Barton, S. & Swinden, J. Occurrence, fate and transformation of emerging contaminants in water: an overarching review of the field. Environ. Pollut. 231, 954–970 (2017).

    CAS  PubMed  Google Scholar 

  83. Matson, C. W. et al. Evolutionary toxicology: population-level effects of chronic contaminant exposure on the marsh frogs (Rana ridibunda) of Azerbaijan. Environ. Health Perspect. 114, 547–552 (2006).

    CAS  PubMed  Google Scholar 

  84. Hinton, D. E. et al. Resolving mechanisms of toxicity while pursuing ecotoxicological relevance? Mar. Pollut. Bull. 51, 635–648 (2005).

    CAS  PubMed  Google Scholar 

  85. Martineau, D. et al. Cancer in wildlife, a case study: beluga from the St. Lawrence Estuary, Québec, Canada. Environ. Health Perspect. 110, 285–292 (2002).

    PubMed  PubMed Central  Google Scholar 

  86. Ellegren, H., Lindgren, G., Primmer, C. R. & Møller, A. P. Fitness loss and germline mutations in barn swallows breeding in Chernobyl. Nature 389, 593–596 (1997).

    CAS  PubMed  Google Scholar 

  87. Herbert, A. et al. European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology. Cytopathology 18, 213–219 (2007).

    CAS  PubMed  Google Scholar 

  88. Buckley, C. H., Butler, E. B. & Fox, H. Cervical intraepithelial neoplasia. J. Clin. Pathol. 35, 1–13 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Randhawa, N., Gulland, F. M., Ylitalo, G. M., DeLong, R. & Mazet, J. A. K. Sentinel California sea lions provide insight into legacy organochlorine exposure trends and their association with cancer and infectious disease. One Health 1, 37–43 (2015). This study highlights how establishing causality in sporadic cancers of wildlife is challenging, in part owing to the extreme variability of comorbidities and in specimen status. This work effectively not only addresses the variation of fat, animal age and animal sex on OC accumulation but also frames it in the context of disease and highlights the nature of this long-lived, apex predator as a source of bioconcentration.

    PubMed  PubMed Central  Google Scholar 

  90. Lair, S., Measures, L. N. & Martineau, D. Pathologic Findings and Trends in Mortality in the Beluga (Delphinapterus leucas) Population of the St Lawrence Estuary, Quebec, Canada, From 1983 to 2012. Vet. Pathol. 53, 22–36 (2016). This study is important, given the multifactorial effects of toxins on cancer formation and reproductive health, as it identifies both malignant tumours and reproductive diseases as contributing to the declining numbers of beluga in this region, a species that, despite efforts of protection, has not recovered over the past several decades.

    CAS  PubMed  Google Scholar 

  91. Jönsson, A., Gustafsson, O., Axelman, J. & Sundberg, H. Global accounting of PCBs in the continental shelf sediments. Environ. Sci. Technol. 37, 245–255 (2003).

    PubMed  Google Scholar 

  92. Mills, P. K. & Yang, R. C. Agricultural exposures and gastric cancer risk in Hispanic farm workers in California. Environ. Res. 104, 282–289 (2007).

    CAS  PubMed  Google Scholar 

  93. Jayaraj, R., Megha, P. & Sreedev, P. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment. Interdiscip. Toxicol. 9, 90–100 (2016).

    CAS  PubMed  Google Scholar 

  94. Koehler, A. The gender-specific risk to liver toxicity and cancer of flounder (Platichthys flesus (L.)) at the German Wadden Sea coast. Aquat. Toxicol. 70, 257–276 (2004).

    CAS  PubMed  Google Scholar 

  95. Annamalai, J. & Namasivayam, V. Endocrine disrupting chemicals in the atmosphere: Their effects on humans and wildlife. Environ. Int. 76, 78–97 (2015).

    CAS  PubMed  Google Scholar 

  96. Bergman, J. J. H. A., Jobling, S., Kidd, K. A. & Zoeller, R. T. (eds) State of the Science of Endocrine Disrupting Chemicals –2012 (WHO-UNEP, 2012).

  97. Sifakis, S., Androutsopoulos, V. P., Tsatsakis, A. M. & Spandidos, D. A. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems. Environ. Toxicol. Pharmacol. 51, 56–70 (2017).

    CAS  PubMed  Google Scholar 

  98. Alavian-Ghavanini, A. & Rüegg, J. Understanding epigenetic effects of endocrine disrupting chemicals: from mechanisms to novel test methods. Basic Clin. Pharmacol. Toxicol. 122, 38–45 (2017).

    PubMed  Google Scholar 

  99. De Roos, A. J. et al. Persistent organochlorine chemicals in plasma and risk of non-Hodgkin’s lymphoma. Cancer Res. 65, 11214–11226 (2005).

    PubMed  Google Scholar 

  100. Jaber, J. R. et al. Hepatosplenic large cell immunoblastic lymphoma in a bottlenose dolphin (Tursiops truncatus) with high levels of polychlorinated biphenyl congeners. J. Comp. Pathol. 132, 242–247 (2005).

    CAS  PubMed  Google Scholar 

  101. Blazer, V. S. et al. Tumors in white suckers from Lake Michigan tributaries: pathology and prevalence. J. Fish Dis. 40, 377–393 (2017).

    CAS  PubMed  Google Scholar 

  102. Ordonez-Moran, P. & Munoz, A. Nuclear receptors: genomic and non-genomic effects converge. Cell Cycle 8, 1675–1680 (2009).

    CAS  PubMed  Google Scholar 

  103. Cowin, P. A. et al. Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism. Endocrinology 151, 783–792 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Liu, Y. et al. Global DNA methylation in gonads of adult zebrafish Danio rerio under bisphenol A exposure. Ecotoxicol. Environ. Saf. 130, 124–132 (2016).

    CAS  PubMed  Google Scholar 

  105. Bhan, A. et al. Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo. J. Steroid Biochem. Mol. Biol. 141, 160–170 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Sun, W., Yang, Y., Xu, C. & Guo, J. Regulatory mechanisms of long noncoding RNAs on gene expression in cancers. Cancer Genetics 217, 105–110 (2017).

    Google Scholar 

  107. Christensen, B. C. & Marsit, C. J. Epigenomics in environmental health. Front. Genet. 2, 84 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Stockinger, B. Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system. J. Biol. 8, 61 (2009).

    PubMed  PubMed Central  Google Scholar 

  109. Hall, A. J. et al. Predicting the effects of polychlorinated biphenyls on cetacean populations through impacts on immunity and calf survival. Environ. Pollut. 233, 407–418 (2017).

    PubMed  Google Scholar 

  110. Xu, T. et al. Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage. Toxicol. Appl. Pharmacol. 277, 183–191 (2014).

    CAS  PubMed  Google Scholar 

  111. Grogan, K. E., Sauther, M. L., Cuozzo, F. P. & Drea, C. M. Genetic wealth, population health: major histocompatibility complex variation in captive and wild ring-tailed lemurs (Lemur catta). Ecol. Evol. 7, 7638–7649 (2017).

    PubMed  PubMed Central  Google Scholar 

  112. Frankham, R., Ballou, J. D. & Briscoe, D. A. Introduction to conservation genetics. (Cambridge University Press, Cambridge, UK, 2010).

    Google Scholar 

  113. Furlan, E. et al. Small population size and extremely low levels of genetic diversity in island populations of the platypus, Ornithorhynchus anatinus. Ecol. Evol. 2, 844–857 (2012).

    PubMed  PubMed Central  Google Scholar 

  114. Manta, L. et al. The etiopathogenesis of uterine fibromatosis. J. Med. Life 9, 39–45 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Vander Wal, E., Garant, D. & Pelletier, F. Evolutionary perspectives on wildlife disease: concepts and applications. Evol. Appl. 7, 715–722 (2014).

    Google Scholar 

  116. Facemire, C. F., Gross, T. S. & Guillette, L. J. Reproductive impairment in the Florida panther: nature or nurture? Environ. Health Perspect. 103, 79–86 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Edwards, T. M., Moore, B. C. & Guillette, L. J. J. Reproductive dysgenesis in wildlife: a comparative view. Int. J. Androl. 29, 109–121 (2006).

    PubMed  Google Scholar 

  118. Agnew, D. W. & Machlachlan, N. J. in Tumors of the Domestic Animals (ed. Meuten, D. J.) 689 (Wiley-Blackwell, 2016).

  119. Veeramachaneni, D. N., Amann, R. P. & Jacobson, J. P. Testis and antler dysgenesis in sitka black-tailed deer on Kodiak Island, Alaska: sequela of environmental endocrine disruption? Environ. Health Perspect. 114, 51–59 (2006).

    PubMed  Google Scholar 

  120. Hope, K. & Deem, S. L. Retrospective study of morbidity and mortality of captive jaguars (Panthera onca) in North America, 1982–2002. Zoo Biol. 25, 501–512 (2006).

    Google Scholar 

  121. Harrenstien, L. A. et al. Mammary cancer in captive wild felids and risk factors for its development: a retrospective study of the clinical behavior of 31 cases. J. Zoo Wildl. Med. 27, 468–476 (1996).

    Google Scholar 

  122. Munson, L. A high prevalence of ovarian papillary cystadenocarcinomas in jaguars [abstract]. Vet. Pathol. 31, 604 (1994).

    Google Scholar 

  123. Corner, S. M., Parys, M., Moresco, A., Yuzbasiyan-Gurkan, V. & Agnew, D. in ACVP & ASVCP Concurrent Annual Meeting (Vancouver, British Columbia, Canada, 2017).

  124. McGowen, M. R., Agnew, D. & Wildman, D. E. in Molecular Population Genetics, Phylogenetics, Evolutionary Biology and Conservation of the Neotropical Carnivores. (ed. Garcia, M. R.) (Nova Science Publishers, Hauppauge, NY, 2011).

    Google Scholar 

  125. Andrews, L. & Mutch, D. G. Hereditary ovarian cancer and risk reduction. Best Pract. Res. Cllin. Obstet. Gynaecol. 41, 31–48 (2017).

    Google Scholar 

  126. Smith, M. J., Williams, R. J. & Purves, D. W. Boosting CITES through research. Science 331, 857–858 (2011).

    CAS  PubMed  Google Scholar 

  127. Penfold, L. M., Powell, D., Traylor-Holzer, K. & Asa, C. S. “Use it or lose it”: characterization, implications, and mitigation of female infertility in captive wildlife. Zoo Biol. 33, 20–28 (2014).

    PubMed  Google Scholar 

  128. Schlafer, D. in Pathology of the Domestic Animals (ed. Maxie, G.) 358–464 (Elsevier, St. Louis, MO, 2015).

    Google Scholar 

  129. Hermes, R., Hildebrandt, T. B. & Goritz, F. Reproductive problems directly attributable to long-term captivity. Anim. Reprod. Sci. 82–82, 49–60 (2004).

    Google Scholar 

  130. Hermes, R., Goritz, F., Saragusty, J., Stoops, M. A. & Hildebrandt, T. B. Reproductive tract tumours: The scourge of woman reproduction ails Indian rhinoceroses. PLoS ONE 9, 1–10 (2014). This work provides an overview of the likely associations and possible causes of reproductive system tumours and the overall impact of these tumours on a single endangered species, providing a model for consideration of the impact cancer may have on other wildlife populations.

    Google Scholar 

  131. Lowenstine, L. J., McManamon, R. & Terio, K. A. Comparative pathology of aging great apes: bonobos, chimpanzees, gorillas, and orangutans. Vet. Pathol. 53, 250–276 (2016).

    CAS  PubMed  Google Scholar 

  132. Chaffee, B. K. et al. Spontaneous reproductive tract lesions in aged captive chimpanzees. Vet. Pathol. 53, 425–435 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Smith, L. N. et al. Reproductive neoplasms in wild and long-term captive female manatees (Trichechus manatus latirostris). J. Zoo Wildl. Med. 46, 895–903 (2015).

    PubMed  Google Scholar 

  134. Walker, C. L. Role of hormonal and reproductive factors in the etiology and treatment of uterine leiomyoma. Recent Prog. Horm. Res. 57, 277–294 (2002).

    CAS  PubMed  Google Scholar 

  135. Styer, A. K. & Rueda, B. R. The epidemiology and genetics of uterine leiomyoma. Best Pract. Res. Cllin. Obstet. Gynaecol. 34, 3–12 (2016).

    Google Scholar 

  136. Ellingjord-Dale, M. et al. Parity, hormones and breast cancer subtypes - results from a large nested case-control study in a national screening program. Breast Cancer Res. 19, 10 (2017).

    PubMed  PubMed Central  Google Scholar 

  137. Munson, L. & Moresco, A. Comparative pathology of mammary gland cancers in domestic and wild animals. Breast Dis. 28, 7–21 (2007). This paper is a comparative study of mammary gland cancers, which provides unique insights into common patterns and possible preventative and therapeutic strategies.

    CAS  PubMed  Google Scholar 

  138. Munson, L., Moresco, A. & Calle, P. P. in Wildlife Contraception: Issues, Methods, and Applications (eds Asa, C. S. & Porton, I. J.) 66–82 (Johns Hopkins Univ. Press, Baltimore, 2005).

    Google Scholar 

  139. McAloose, D., Munson, L. & Naydan, D. K. Histologic features of mammary carcinomas in zoo felids treated with melengestrol acetate (MGA) contraceptives. Vet. Pathol. 44, 320–326 (2007).

    CAS  PubMed  Google Scholar 

  140. Osmond, M. M., Otto, S. P. & Klausmeier, C. A. When predators help prey adapt and persist in a changing environment. Am. Nat. 190, 83–89 (2017).

    PubMed  Google Scholar 

  141. Ujvari, B., Gatenby, R. A. & Thomas, F. The evolutionary ecology of transmissible cancers. Infect., Genet. Evol. 39, 293–303 (2016). This paper explains how the potential impact transmissible tumours may have on populations has likely been underestimated and details what is known and needs to be uncovered about these biologically interesting and potentially species-threatening cancers.

    Google Scholar 

  142. Siddle, H. V. & Kaufman, J. Immunology of naturally transmissible tumours. Immunology 144, 11–20 (2015).

    CAS  PubMed  Google Scholar 

  143. Park, M. S. et al. Disseminated transmissible venereal tumor in a dog. J. Vet. Diagn. Invest. 18, 130–133 (2006).

    PubMed  Google Scholar 

  144. Frampton, D. et al. Molecular signatures of regression of the canine transmissible venereal tumor. Cancer Cell 33, 620–633 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Nowinsky, M. Zur Frage ueber die Impfung der krebsigen Geschwuelste. Zentralbl Med. Wiss. 14, 790–791 (1876).

    Google Scholar 

  146. Hawkins, C. E. et al. Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii. Biol. Conserv. 131, 307–324 (2006).

    Google Scholar 

  147. Wells, K. et al. Infection of the fittest: devil facial tumour disease has greatest effect on individuals with highest reproductive output. Ecol. Lett. 20, 770–778 (2017).

    PubMed  Google Scholar 

  148. Pye, R. J. et al. A second transmissible cancer in Tasmanian devils. Proc. Natl Acad. Sci. USA 113, 374–379 (2016).

    CAS  PubMed  Google Scholar 

  149. Siddle, H. V. et al. Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proc. Natl Acad. Sci. USA 110, 5103–5108 (2013).

    CAS  PubMed  Google Scholar 

  150. Ujvari, B. & Belov, K. Major Histocompatibility Complex (MHC) markers in conservation biology. Int. J. Mol. Sci. 12, 5168–5186 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Stammnitz, M. R. et al. The origins and vulnerabilities of two transmissible cancers in Tasmanian devils. Cancer Cell 33, 607–619 (2018). This paper refers to DFTD, which is a threat to the survival of the Tasmanian devil, and reveals how these tumours are providing useful models to understand carcinogenesis in novel and informative ways.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Metzger, M. J. et al. Widespread transmission of independent cancer lineages within multiple bivalve species. Nature 534, 705–709 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Muehlenbachs, A. et al. Malignant transformation of Hymenolepis nana in a human host. N. Engl. J. Med. 373, 1845–1852 (2015).

    CAS  PubMed  Google Scholar 

  154. Conn, D. B. Malignant transformation of Hymenolepis nana in a human host. N. Engl. J. Med. 374, 1293 (2016).

    PubMed  Google Scholar 

  155. Abegglen, L. M. et al. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. J. Am. Vet. Med. Assoc. 314, 1850–1860 (2015).

    CAS  Google Scholar 

  156. Pessier, A. P., Stern, J. K. & Witte, C. L. TP53 gene and cancer resistance in elephants. JAMA 315, 1789 (2016).

    PubMed  Google Scholar 

  157. Roher, D. P. & Nielsen, S. W. Carcinoma in the urinary bladder of a white-tailed deer (Odocoileus virginianus). J. Wildl. Dis. 18, 361–363 (1982).

    CAS  PubMed  Google Scholar 

  158. Wobeser, G. & Wobeser, A. G. Carcass disappearance and estimation of mortality in a simulated die-off of small birds. J. Wildl. Dis. 28, 548–554 (1992). This article describes the substantial rate of carcass attrition and highlights the difficulty in detecting moribund or dead animals — one of the greatest challenges in wildlife disease surveillance — which is likely exacerbated in instances with a relatively low prevalence of disease at a given time.

    CAS  PubMed  Google Scholar 

  159. Beringer, J., Hansen, L. P. & Stallknech, D. E. An epizootic of hemorrhagic disease in white-tailed deer in Missouri. J. Wildl. Dis. 36, 588–591 (2000).

    CAS  PubMed  Google Scholar 

  160. Moresco, A. & Agnew, D. W. Reproductive health surveillance in zoo and wildlife medicine. J. Zoo Wildl. Med. 44, S26–33 (2013).

    PubMed  Google Scholar 

  161. Karlitz, J. J. et al. Colorectal cancer incidence rates in the Louisiana Acadian Parishes demonstrated to be among the highest in the United States. Clin. Transl Gastroenterol. 5, e60 (2014).

    PubMed  PubMed Central  Google Scholar 

  162. Mantere, T. et al. Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer. Clin. Genet. 88, 68–73 (2015).

    CAS  PubMed  Google Scholar 

  163. Im, K. M. et al. Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers. Hum. Genet. 130, 685–699 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Belanger, M. H. et al. A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population. J. Ovarian Res. 8, 1 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Favé, M. J. et al. Gene-by-environment interactions in urban populations modulate risk phenotypes. Nat. Commun. 9, 827 (2018).

    PubMed  PubMed Central  Google Scholar 

  166. Caulin, A. F. & Maley, C. C. Peto’s Paradox: evolution’s prescription for cancer prevention. Trends Ecol. Evol. 26, 175–182 (2011).

    PubMed  PubMed Central  Google Scholar 

  167. Seluanov, A., Gladyshev, V. N., Vijg, J. & Gorbunova, V. Mechanisms of cancer resistance in long-lived mammals. Nat. Rev. Cancer (2018).

  168. Koch, R. Die Aetiologie der Tuberkulose. Mitt. k. Gesundh-Amte 2, 1–88 (1884).

    Google Scholar 

  169. Hill, A. B. The environment and disease: association or causation? Proc. R. Soc. Med. 58, 295–300 (1965).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Kean, J. M., Rao, S., Wang, M., Garcea, R. L. & Atwood, W. J. Seroepidemiology of human polyomaviruses. PLoS Pathol. 5, e1000363 (2009).

    Google Scholar 

  171. Namiesnik, J. et al. Concentration of bioactive compounds in mussels Mytilus galloprovincialis as an indicator of pollution. Chemosphere 73, 938–944 (2008).

    CAS  PubMed  Google Scholar 

  172. Kakehashi, A., Wei, M., Fukushima, S. & Wanibuchi, H. Oxidative stress in the carcinogenicity of chemical carcinogens. Cancers 5, 1332–1354 (2013).

    PubMed  PubMed Central  Google Scholar 

  173. Spink, D. C. et al. Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: roles of PAH interactions and PAH metabolites. Toxicol. Appl. Pharmacol. 226, 213–224 (2008).

    CAS  PubMed  Google Scholar 

  174. Tarantini, A. et al. Relative contribution of DNA strand breaks and DNA adducts to the genotoxicity of benzo[a]pyrene as a pure compound and in complex mixtures. Mutat. Res. 671, 67–75 (2009).

    CAS  PubMed  Google Scholar 

  175. Chaudhuri, L. et al. Polychlorinated biphenyl induced ROS signaling delays the entry of quiescent human breast epithelial cells into the proliferative cycle. Free Radic. Biol. Med. 49, 40–49 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Ng, H. W., Perkins, R., Tong, W. & Hong, H. Versatility or promiscuity: the estrogen receptors, control of ligand selectivity and an update on subtype selective ligands. Int. J. Env. Res. Publ. Health 11, 8709–8742 (2014).

    CAS  Google Scholar 

  177. Karoutsou, E., Karoutsos, P. & Karoutsos, D. Endocrine disruptors and carcinogenesis. Arch. Canc. Res. 5, 1–8 (2017).

    Google Scholar 

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Acknowledgements

The authors are grateful to B. Stacy (University of Florida), K. Colegrove (University of Illinois) and S. L. Quackenbush (University of Colorado) for responding to their requests for additional information and to J. Crum (West Virginia Division of Natural Resources) for his contribution of cancer cases in white-tailed deer. The authors are also deeply grateful to their colleagues at the University of California Davis and Michigan State University, East Lansing, for comments on the manuscript and their support.

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Nature Reviews Cancer thanks A. Boddy, J. Landolfi and D. McAloose for their contribution to the peer review of this work.

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In addition to contributions in research, P.A.P., D.A. and K.D.W. all contributed to the writing, reviewing and editing of the manuscript. M.K.K. was instrumental in drafting the manuscript and in providing observations from morbidity and mortality investigations.

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Correspondence to Patricia A. Pesavento.

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Glossary

Canine distemper virus

An enveloped single-stranded negative RNA virus of the family Paramyxoviridae related to the viruses that cause measles in humans. It is also referred to as carnivore distemper virus, as it causes systemic disease in a wide variety of animal families, including domestic and wild dogs, coyotes, foxes, pandas, wolves, ferrets, skunks, raccoons, large cats and pinnipeds.

Fibropapilloma

A condition characterized by the presence of proliferative benign neoplasms containing superficial epidermal and subjacent dermal tissue.

Cloaca

The caudal opening in reptiles, amphibians and birds used for digestive, reproductive and urinary tract excretions.

Retroviruses

RNA viruses that utilize reverse transcriptase to generate a complementary DNA strand from the RNA template, which is then integrated into the genome of the infected cell.

Nasal conchae

Also called nasal turbinates. Convoluted, curled thin bones covered by respiratory epithelium that protrude into the breathing passage of animals.

Ectotherms

Animals dependent on exogenous heat to maintain body temperature.

Agrarian

Relating to farmland, agriculture or the cultivation of land for crops.

Xenobiotics

Any substance (synthetic or natural) that is not naturally present in the body of an organism.

Endocrine disrupting compounds

(EDCs). A broad category of mostly man-made substances that are present in pesticides, plastics, personal care products, metals and pharmaceuticals, among many other items, which result in altered hormonal activity via agonistic and antagonistic receptor binding.

Bioaccumulate

When a substance becomes concentrated within the body of a living thing. If the source of the substance is from water, this is specifically referred to as bioconcentration.

Biomagnify

The increasing concentration of a substance within the tissues of an organism acquired through predatory acquisition (a food chain).

Benthic zone

The lowest ecological regions of a body of water, such as the sediment surface.

Evolutionary mismatch

A concept in evolutionary biology referring to the presence of once beneficial traits in a population that, owing to rapid environmental change, are no longer beneficial but harmful.

Cryptorchidism

The absence of one or both testes from the scrotum, usually resulting from a failure to descend during development.

Seminomas

A type of germ cell tumour of the testicle.

Sertoli cell tumours

A sex cord-gonadal stromal tumour composed of Sertoli cells, which line the seminiferous tubules and help in the development of sperm. These are typically benign and often hormonally active.

Estrous cycle

The recurring cyclic variation in reproductive hormones (for example, oestrogen and progesterone) in the mammalian female that controls behaviour, reproductive organ morphology, ovulation and conception.

Leiomyomas

When present in the reproductive tract (vagina, cervix, uterus, oviduct or ovary), these are hormonally responsive benign smooth muscle tumours. In humans, these are also known as fibroids.

Cystic endometrial hyperplasia

A condition of excessive proliferation of the glandular epithelium of the uterus, typically associated with excessive progesterone and/or oestrogen stimulation.

Nulliparous

An animal that has never given birth.

Multiparous

An animal that has given birth multiple times.

Diestrus

A non-receptive phase of the estrous cycle dominated by progesterone production.

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Pesavento, P.A., Agnew, D., Keel, M.K. et al. Cancer in wildlife: patterns of emergence. Nat Rev Cancer 18, 646–661 (2018). https://doi.org/10.1038/s41568-018-0045-0

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