The molecular mechanisms of how n-3 PUFA excert anticancer properties are not well understood. Thus, the cancer chemopreventive properties of EPA and DHA were the core subject of in vitro studies. Furthermore, samples (n=89) of the first randomised controlled human trial intervening with lean and oil-rich fish, the FISHGASTRO trial, were screened ex vivo for markers of chemoprevention. It was shown that EPA and DHA impair cell growth and induce apoptosis. Gene expression was affected in a time- and substance-specific manner. Overall, genes connected with biotransformation, cell cycle control, signalling pathways, apoptosis, and inflammation were altered. More specifically, SOD2 induction and probably an enhanced peroxidase activity due to GSTT2 induction indicate reduction of oxidative stress. Whereas GSTT2 was induced by EPA it was reduced by DHA in HT29 cells. Anti-inflammatory activity can be attributed to COX-2 decrease by DHA in both cell types. In contrast, EPA induced COX-2 in LT97 cells. It was not possible to prove that faecal water (FW)-incubated LT97 cells were an appropriate source for biomarker identification to test the hypothesis that additional consumption of fish is beneficial for gut health. There was no marked alteration of genotoxicity or apoptosis by fish-intervention. The evidence of the comparably small impact of FW on the modulation of global gene expression in LT97 cells and the influence of an additional consumption of fish still require final assessment. The extent to which these findings may be related to a lack of impact of oil-rich fish needs further clarification. In conclusion it was shown, that EPA and DHA exert chemopreventive properties in vitro. As the results from the human intervention study were not appropriate to judge the in vivo situation, there is still a need to prove the hypothesis that oil-rich fish acts in a colon cancer chemopreventive manner.