Environmental factors can cause cancer in both wild animals and humans. In ecological settings, genetic variation and natural selection can sometimes produce resilience to the negative impacts of environmental change. An increase in oncogenic substances in natural habitats has therefore, unintentionally, created opportunities for using polluted habitats to study cancer defence mechanisms. The Baltic and North Sea are among the most contaminated marine areas, with a long history of pollution. Two flatfish species (flounder, Platichthys flesus and dab, Limanda limanda) are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is more prevalent in dab, suggesting species-specific differences in vulnerability and/or defence mechanisms. We conducted gene expression analyses for 30 flatfishes. We characterize between- and within-species patterns in potential cancer-related mechanisms. By comparing cancerous and healthy fishes, and non-cancerous fishes from clean and polluted sites, we suggest also genes and related physiological mechanisms that could contribute to a higher resistance to pollution-induced cancer in flounders. We discovered changes in transcriptome related to elevated pollutant metabolism, alongside greater tumour suppression mechanisms in the liver tissue of flounders compared to dabs. This suggests either hormetic upregulation of tumour suppression or a stronger natural selection pressure for higher cancer resistance for flounders in polluted environment. Based on gene expression patterns seen in cancerous and healthy fish, for liver cancer to develop in flounders, genetic defence mechanisms need to be suppressed, while in dabs, analogous process is weak or absent. We conclude that wild species could offer novel insights and ideas for understanding the nature and evolution of natural cancer defence mechanisms.

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists. Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine. The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations. There are still a number of challenges in collecting cancer data from wild animals. This paper provides a review of currently available methods to detect and measure cancer in wild organisms as well as the methodological limitations to be overcome to develop approaches inspired by diagnostic techniques used in human medicine.image

Many species in aquatic environments face increased exposure to oncogenic pollution due to anthropogenic environmental change which can lead to higher cancer prevalence. The mechanistic relationship connecting environmental pollution and cancer is multi-factorial and poorly understood, and the specific mechanisms are so far still uncharacterized. One potential mediator between pollutant exposure and cancer is oxidative damage to DNA. We conducted a study in the field with two flatfish species, European flounder (Platichthys flesus L.) and common dab (Limanda limanda L.) with overlapping distribution and similar ecological niche, to investigate if the link between oncogenic pollutants and cancer described in ecotoxicological literature could be mediated by oxidative DNA damage. This was not the case for flounders as neither polycyclic aromatic hydrocarbon (PAH) bile metabolites nor metallic trace element concentrations were related to oxidative DNA damage measurements. However, dabs with higher PAH concentrations did exhibit increased oxidative damage. High oxidative DNA damage also did not predict neoplasm occurrence, rather, healthy individuals tended to have higher oxidative damage measurements compared to fishes with pre-neoplastic tumours. Our analyses showed that flounders had lower concentrations of PAH bile metabolites, suggesting that compared to dab this species is less exposed or better at eliminating these contaminants.

Environmental factors cause cancer in both wild animals and humans. In ecological settings, genetic variation and natural selection can produce resilience to the negative impacts of environmental change. An increase in oncogenic substances in natural habitats has therefore, unintentionally, created opportunities for using polluted habitats to study cancer defence mechanisms. The Baltic and North Sea are amongst the most contaminated marine areas, with a long history of pollution. Two flatfish species (flounder, Platichthys flesus and dab, Limanda limanda) are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is more prevalent in dab, suggesting species-specific differences in vulnerability and/or defence mechanisms. We conducted gene expression analyses for 28 flatfishes. By comparing cancerous and healthy fishes, and non-cancerous fishes from clean and polluted sites, we suggest genes and related physiological mechanisms that could contribute to a higher resistance to pollution-induced cancer in flounders. We discovered changes in transcriptome related to elevated pollutant metabolism, alongside greater tumour suppression mechanisms in the liver tissue of flounders compared to dabs. This suggests that in flounders, either hormetic upregulation of tumour suppression or a stronger natural selection pressure for higher cancer resistance has evolved in a polluted environment. For pollution-induced liver cancer to develop in flounders, genetic defence mechanisms need to be suppressed, while in dabs, analogous process is weak or absent in our samples. We conclude that wild species could offer novel insights and ideas for understanding the nature and evolution of natural cancer defence mechanisms.

Comparative studies of cancer-related genes allow us to gain novel information about the evolution and function of these genes, but also to understand cancer as a driving force in biological systems and species life histories. So far, comparative studies of cancer genes have focused on mammals. Here, we provide the first comparative study of cancer-related gene copy number variation in fish. As fish are evolutionarily older and genetically more diverse than mammals, their tumour suppression mechanisms should not only include most of the mammalian mechanisms, but also reveal novel (but potentially phylogenetically older) previously undetected mechanisms. We have matched the sequenced genomes of 65 fish species from the Ensemble database with the cancer gene information from the COSMIC database. By calculating the number of gene copies across species using the Ensembl CAFE data (providing species trees for gene copy number counts), we were able to develop a novel, less resource demanding method for ortholog identification. Our analysis demonstrates a masked relationship with cancer-related gene copy number variation (CNV) and maximum lifespan in fish species, suggesting that higher tumour suppressor gene CNV lengthens and oncogene CNV shortens lifespan, when both traits are added to the model. Based on the correlation between tumour suppressor and oncogene CNV, we were able to show which species have more tumour suppressors in relation to oncogenes. It could therefore be suggested that these species have stronger genetic defences against oncogenic processes. Fish studies could yet be a largely unexplored treasure trove for understanding the evolution and ecology of cancer, by providing novel insights into the study of cancer and tumour suppression, in addition to the study of fish evolution, life-history trade-offs, and ecology.

Due to the interconnectedness of aquatic ecosystems through the highly effective marine and atmospheric transport routes, all aquatic ecosystems are potentially vulnerable to pollution. Whilst links between pollution and increased mortality of wild animals have now been firmly established, the next steps should be to focus on specific physiological pathways and pathologies that link pollution to wildlife health deterioration. One of the pollution-induced pathologies that should be at the centre of attention in ecological and evolutionary research is cancer, as anthropogenic contamination has resulted in a rapid increase of oncogenic substances in natural habitats. Whilst wildlife cancer research is an emerging research topic, systematic reviews of the many case studies published over the recent decades are scarce. This research direction would (1) provide a better understanding of the physiological mechanisms connecting anthropogenic pollution to oncogenic processes in non-model organisms (reducing the current bias towards human and lab-animal studies in cancer research), and (2) allow us to better predict the vulnerability of different wild populations to oncogenic contamination. This article combines the information available within the scientific literature about cancer occurrences in aquatic and semi-aquatic species. For the first aim, we use available knowledge from aquatic species to suggest physiological mechanisms that link pollution and cancer, including main metabolic detoxification pathways, oxidative damage effects, infections, and changes to the microbiome. For the second aim, we determine which types of aquatic animals are more vulnerable to pollution-induced cancer, which types of pollution are mainly associated with cancer in aquatic ecosystems, and which types of cancer pollution causes. We also discuss the role of migration in exposing aquatic and semi-aquatic animals to different oncogenic pollutants. Finally, we suggest novel research avenues, including experimental approaches, analysis of the effects of pollutant cocktails and long-term chronic exposure to lower levels of pollutants, and the use of already published databases of gene expression levels in animals from differently polluted habitats.