Gidoin Cindy auteur aut IRD Ujvari B. auteur aut IRD Thomas F. auteur aut IRD Roche Benjamin auteur aut IRD text journalArticle eng text/pdf reformatted digital access Background : A strong variability in cancer incidence is observed between human organs. Recently, it has been suggested that the relative contribution of organs to organism fitness (reproduction or survival) could explain at least a part of the observed variation. The objective of this study is to investigate theoretically the main factors driving the evolution of tumour resistance mechanisms of organs when their relative contribution to organism fitness is considered. We use a population-scale model where individuals can develop a tumour in a key organ (i.e. in which even a small tumour can negatively impact organism fitness), an auxiliary organ (i.e. in which only a large tumour has a relatively significant impact) or both organs because of metastasis. Results : Our simulations show that natural selection acts in two different ways to prevent cancer in a key and an auxiliary organs. In the key organ, the strategy mostly selected is the highest resistance and only a high cost of resistance mitigates this behavior. Inversely, we observe that a low resistance strategy can be selected in the auxiliary organ when the development of the tumour is slow and the effect of a large tumour on the mortality of the organism is relatively weak. Nevertheless, if the tumour can spread to a key organ, higher resistance strategies are selected in the auxiliary organ. Conclusion : Finally, our study demonstrates that the relative contribution of organs to the organism fitness and the metastatic propensity of the tumour influence the evolution of tumour resistance at organ scale and should be considered by studies aiming to explain the variability in cancer incidence at organ-scale. specialized Trade-off Metastasis Cancer risk Tumorigenesis 050 020 18 art. 185 [10 ] 2018 1471-2148 https://www.documentation.ird.fr/hor/fdi:010074748 10.1186/s12862-018-1298-7 1471-2148 [F B010074748] https://www.documentation.ird.fr/hor/fdi:010074748 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers18-12/010074748.pdf IRD - Base Horizon / Pleins textes 2019-01-10 2023-07-11 fdi:010074748 fre