The Epigenomics and Mechanisms branch at IARC (headed by Dr Z. Herceg) has a long-standing interest in understanding the origins and causes of childhood cancer. An important emphasis of the team has been on studies aimed at understanding molecular precursors of cancers in children by investigating epigenetic changes associated with risk factors and identifying epigenetic biomarkers for cancer risk stratification and early detection. The focus is on the in utero and early-life period, when the impact of health risk factors is particularly important, potentially with lifelong consequences. The team builds on its recent advances in identifying epigenetic markers of early-life factors and deciphering their precursor roles in childhood cancer and its predisposing (intermediate) phenotypes at critical ages of development as well as capitalizing on the unique and complementary networks of prospective and retrospective consortia that are particularly instrumental in these studies.

Furthermore, the team has been increasingly adopting innovative study designs that overcome statistical power limitations associated with rare diseases such as childhood cancer. These developments enabled their studies that provide critical insights into causes and biomarkers of risk that should prove important in implementing new strategies for prevention and therapy. The impetus for these scientific projects was provided by significant methodology development in the wet and dry-lab components of the team, encompassing methods in -omics (notably epigenomics and transcriptomics) profiling, molecular epidemiology, molecular biology, bioinformatics, and biostatistics.

Their major role and access to international networks and consortia facilitated the development of a multifaceted research program aimed at identifying epigenetic changes associated with risk factor exposures relevant to the occurrence of cancer in children and young adults and providing biological plausibility for the associations that are detected in epidemiological studies. The team will contribute to the WP1 (identify childhood cancer risk factors) with the lead role in Task 3 (Epigenetic markers as molecular mediators between the effect of exposure and childhood cancer risk).

Specifically, the analysis will focus on three subtasks:
– epigenetic markers of exposures in mother-child cohorts,
– relationship between epigenetic markers and childhood cancer in nested case-control studies .
– the team will also make an important contribution to WP3 (integrated molecular bases on childhood cancer) with a role in Task 1 (intrinsic factors driving childhood cancer), where the study will focus on identifying epigenetic regulators and key genes on tumor cell maintenance and identity, and Task 3 (pediatric tumor ecosystem reconstruction) where the team will participate in the technological development to model human tumor site ecosystem.