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Epigenetic Variation as a Driver of Breast Cancer Risk
Imperial College London

Genetic epidemiology aims to use the natural variation in the genome to look for associations between particular genotypes and disease risk or prognosis. Epigenetic epidemiology, a new area of research, aims to address the same questions about disease risk and prognosis using the natural variation present in the epigenome. It is now apparent that the variation between individuals does not occur at the classical promoter CpG island, but in other areas of the gene and that these regions are yielding markers of both cancer risk and prognosis. We have identified a breast cancer risk marker in the ATM gene using blood samples collected from prospective cohorts. We have also analysed blood samples from an ovarian cancer clinical trial, SCOTROC1, to identify prognostic biomarkers of progression free survival, overall survival, response and toxicity. Lastly, we have also shown that cancer risk exposures, such as smoking, can affect the epigenome detectable in blood DNA and may provide a more accurate measure of long term exposures. These studies, therefore, support the hypothesis that epigenetic variation may be a driver of cancer risk or prognosis.

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