flounder dab pollution clean cancer liver transcriptome. Cancer-related gene expression in flatfish: potential indication of adaptation to oncogenic pollution?

Tackling cancer is considered a global challenge that calls for integration of diverse fields, and studying cancer in wild species in ecological settings is one yet underexplored direction. Majority of human cancers are caused by environmental factors, including oncogenic pollutants, which have also been shown to cause cancer in wild animals. In ecological settings, natural selection can produce solutions to negative impacts of environmental change, given enough time. The increase of oncogenic substances in natural habitats has therefore unintentionally created opportunities for using polluted habitats as “natural laboratories” for studying cancer defence mechanisms. The Baltic and North Sea are among the most polluted marine areas, having a long history of contamination. The populations of two flatfish species (Platichthys flesus and Limanda limanda) inhabit a whole gradient of contamination, creating opportunities for studying populations that have, for a long time, been exposed to differing selection pressures. Both species are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is much more prevalent in dab, suggesting that flounders are better protected against pollution-induced cancer. Here, we have conducted gene expression analyses for 28 flatfish, including flounders and dabs from clean and polluted sites, some with and some without cancer. The results indicate that cancer is more prevalent among dabs than flounders, suggesting natural selection towards cancer-resistant phenotype in flounders living in polluted sites. By comparing non-cancerous fish from clean and polluted sites, we were able to suggest genes and related physiological mechanisms that could be behind higher resistance to pollution-induced cancer in flounders.