The ERC AdG 232635 project Epigenome and Cancer Susceptibility (“Episusceptibility”) focuses on early detection and prevention of cancer – factors that largely determine the outcome of most cancers. We aim to construct a comprehensive view of the stepwise process through which common human cancers, such as colorectal cancer, arise.

In particular, we aim to identify novel mechanisms of cancer susceptibility by concentrating on the epigenome, whose alterations may underlie several phenomena related to chronic adult-onset disease that are not explained by genetics alone. The stepwise process of carcinogenesis can be accelerated or halted for various reasons, including inherited susceptibility and diet. The human multi-organ cancer syndromes hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) as well as their murine counterparts, the Mlh1+/- mouse and the ApcMin/+ mouse, are used as shortcuts to study the interplay between the epigenome and genome in tumorigenesis and to identify biomarkers of cancer susceptibility, malignant transformation, and tumor progression by global and targeted molecular approaches.

Additionally, the role that the epigenome plays to mediate the effects of diet on colorectal tumorigenesis is examined in the mouse. Contrary to previous studies which have typically focused on one aspect at a time, our approach aims to provide a synthesis of interactions between all major players in common human cancers, covering endogenous and exogenous causes of cancer, the genome and epigenome as targets, and most major anatomic sites of adult cancer. Unlike genetic changes, epigenetic alterations are potentially reversible, which makes them promising targets for preventive and therapeutic interventions.