About 2 to 4% of all cancers have an established genetic origin, due to the association of hereditary gene mutations with higher cancer risk. Though the etiology of the remaining cancers is elusive, it is estimated that about 80% have an identifiable cause related to lifestyle or environment. Compelling evidence for the implication of specific environmental factors and lifestyles (non-hereditary “cause”) in tumor development, however, is available for only a small subset of cancers. This represents a major curb on the strategies of cancer prevention.

Recent findings suggest that environmental factors and lifestyles implicated in tumor development might increase cancer risk by inducing alterations of chromatin (epigenomic modifications or epimutations) without causing changes in the underlying DNA sequence. On the other hand, a large body of evidence is emerging to suggest that epigenomic changes are causally linked to oncogenesis and tumor progression.  Thus, epigenomic changes might represent ideal molecular markers of the carcinogenic effects of specific environmental factors and lifestyles.

One critical issue in analyzing the early epigenomic effects of cancer-associated environmental factors and lifestyles is the choice of the cell target. Since the target cell must survive long enough in the human tissues to allow accumulation of genomic damage, tissue stem cells are obvious candidates notably, comparison between the epigenetic characteristics of cancer cells and stem cells suggest that epigenetic deregulation may program stem cells for cancer-like behavior long before they are visually identifiable as tumor cells.

We will test the hypothesis that environmental factors and lifestyles increase the risk of cancer development by inducing specific epigenomic changes tissue stem cells. We expect that this epigenomic changes might then be used as molecular markers for the quantitation of the environmental risk of cancer.  We will pursue this goal by setting-up a number of suitable cancer models for the study of the carcinogenic effects of lyfestyle and environment (obesity, inflammation, UV, aging).