Epigenetic Variation as a Driver of Breast Cancer Risk
Conference Recording Feb 14, 2014
About the Speaker
Dr James Flanagan, completed his PhD in 2002 at QIMR, and has pursued postdoctoral work in Cancer Genetics, Epigenetics and Cancer Epigenetics. He is currently leading his own group as a Breast Cancer Campaign Scientific Fellow in the Epigenetics Unit, Dept of Surgery and Cancer, Imperial College London. He was awarded the British Association of Cancer Research Translational Researcher Award in 2011. Current research is aimed at investigating epigenetic alterations as a mechanism for carcinogenesis, including projects to define tumour subgroups, identification of biomarkers for cancer risk or prognosis in breast and ovarian cancer and investigating the mechanism of transcriptional regulation by DNA methylation outside of the classical promoter CpG Island. Recent work has focussed on the hypothesis that epigenetic variation may be a driver of cancer risk whether by inherent constitutional variation or as a mediator of other cancer risk factors.
Abstract 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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