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EARLY LIFE EVENTS AND EPIGENETIC REPROGRAMMING ASSOCIATED WITH CANCER RISK IN CHILDHOOD AND ADULTHOOD

The broad, long-term goal of Zdenko Herceg’s Group is to advance the understanding of mechanisms of carcinogenesis and to contribute to cancer prevention. To this end, his research efforts continue to investigate interactions between the genes, the epigenome and the environment. In addition, in collaboration with epidemiology groups, his Group contributes to the development of translational studies through the discovery and validation of biomarkers of tumorigenesis and environmental exposures. Another focus of his Group is the development of genetic/epigenetic methods that are applicable to biobanks associated with case-control and population-based studies. The preventive strategies that exploit the possibility of counteracting epigenetic changes can be pushed further. One of these new initiatives in his research addresses the concept of developmental reprogramming of adult cancers.

As Dr Herceg specifies, "During fertilization embryonic stem cells differentiate into the different cell lineages and this is a mainly epigenetic affair. This reprogramming occurs at certain windows of susceptibility, and because it is quite a dramatic genome-wide exercise, these stages of reprogramming may be susceptible to environmental conditions. The idea is that the epigenome undergoes profound reconfiguration during embryonic life. But these changes could also have an impact, not only on embryonic development, but also on childhood and adulthood. This makes sense since the epigenetic changes although potentially reversible, can be propagated with high fidelity over a life course. For example, the changes which may be introduced in the epigenome at early life, may be fixed in a specific cell type (stem cells, progenitors) and may remain silent for months or years until exposed to specific stresses or exposures would be critical for expression of these genes. One can imagine such a scenario involving sex hormone expression in puberty”.

Dr Herceg explains: “We are looking at whether these early life events could be detected at birth at the level of the epigenome, and whether this could predict the exposure during in utero life as well as the risk of cancer in childhood and/or adulthood. To address this question we are participating in an international effort, the International Childhood Cancer Cohort Consortium (I4C), which provides an ideal framework for this study: cohorts from different countries, sample size (statistical power) and information about the exposure and the risks. These are also long-term studies. We are setting up methodologies compatible with these cohorts and their associated biobanks. It is a challenging project and we are at the early stage, however the preliminary findings are encouraging”. Dr Herceg concludes that these studies can be applied to other complex human diseases as well.