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ECAP Report Summary

Project ID: 340588
Funded under: FP7-IDEAS-ERC
Country: Switzerland

Mid-Term Report Summary - ECAP (Genetic/epigenetic basis of ethnic differences in cancer predisposition)

A wealth of epidemiological and clinical data point to significant disparities in incidence and survival of various cancer types among populations of various ethnicities. In particular, individuals of Black African ancestry have a globally higher susceptibility to malignant cancer development and progression than individuals of Caucasians and Asian background. These differences can only be partially explained by differences in life style and access to health care, and concurrent genetic and epigenetic determinants are likely involved. Elucidation of ethnic-specific differences involved in control mechanisms of intrinsic cancer stem cell renewal and of the cancer-promoting stromal microenvironment can be of substantial benefit for development of ethnicity-adapted cancer screening programs and clinical approaches to reduce cancer burden. Work supported by the present grant is aimed at elucidating ethnic differences in determinants of squamous cell carcinoma (SCC) development, the most frequent type of solid human tumors and main cause of death, with skin as model system. It is well known that pigmentation has an important protective role against UV-induced skin SCCs. While individuals of Black African ancestry, with their highly pigmented skin, have a low incidence of skin SCCs, they develop skin SCCs at wound healing sites that are much more aggressive than in Caucasians, with frequent invasion and metastasis.
By combined transcriptomic, genetic and epigenetic approaches, coupled with bioinformatics and statistical analysis, we have identified > 300 differently expressed genes (DEGs) in the intact epidermis, primary human dermal fibroblasts (HDFs) and/or primary human keratinocytes (HKCs) derived from a cohort of individuals of Caucasian versus Black African ethnicities. Initial in vitro and in vivo experiments with a subset of cells derived from these individuals suggest that the differences that we have identified are of functional significance for intrinsic control of cancer stem cell populations as well as for the cancer-promoting properties of surrounding stromal fibroblasts. As such, our work seems likely to provide new ground-breaking insights into ethnic differences in cancer susceptibility.

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