<b>Results:</b> In colon tissues from acute, chronic colitis and CRC mouse models and from CD patients, the biomarkers γH2AX and 53BP1<sub>pS25/S29</sub> of DNA breaks (mainly representing DSBs) accumulated, alongside increases in topoisomerase II (TOP2) and nitric oxide synthase 2 (NOS2). Here, TP53BP1 is linked to Cowden disease.