herenciageneticayenfermedad: Clinical Epigenetics

miércoles, 7 de noviembre de 2018

Clinical Epigenetics | Home page

Clinical Epigenetics | Home page

Clinical Epigenetics

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Breast Cancer Awareness Month

Article Overview by James Flanagan
Epigenetic Age and Risk of Breast Cancer, James Flanagan, Imperial College London

There has been considerable work over the last few years trying to identify DNA methylation biomarkers of breast cancer risk in blood DNA using the Illumina 450k array and more recently the methylationEPIC (850k) array. Some studies, such as ours (PMID:26244061) have identified an overall genome-wide hypomethylation in blood DNA associated with breast cancer risk, while other studies have not replicated this finding. More recently, the idea of an “epigenetic clock”, “age acceleration” or “biological aging” has been explored in an increasing large number of areas and it is starting to gain traction in cancer risk studies.

What is the mechanistic cause of an increased epigenetic age? There are now many studies reporting correlations with epigenetic age ranging from lifestyle factors, such as obesity, menopause, tobacco and alcohol consumption, to stress and even violence in children. However, it is important to note that correlation does not equal causation, and it will require carefully designed intervention studies to pin down the real mechanisms driving the inter-individual variation in “epigenetic age”. Importantly, it has also been associated with increased mortality due to cardiovascular disease and cancer. It makes sense that if you are biologically 70 years old, then your risk of disease or mortality will match that of a 70 year old, rather than the healthy 65 year old that you might otherwise be. The same can be seen with risk of breast cancer, which we know increases with increasing age. In a study by Ambatipudi and colleagues (PMID: 28259012) the increased epigenetic age was associated with increased risk of postmenopausal breast cancer. In a recent study in Clinical Epigenetics by Hofstatter and colleagues(PMID:3015795) they showed that the increased epigenetic age could be observed in normal breast tissue of cancer patients compared with normal breast tissue of non-cancer patients. This is a very important finding as it shows that epigenetic age is an important factor in the tissue of origin of the disease.

However, there is much that remains to be investigated in this area. Is an individual who is epigenetically older in their breast tissue also epigenetically older in their blood DNA. In other words, is epigenetic age itself tissue specific or is blood DNA an appropriate surrogate for other tissues? Is it stable over time and needs measuring just once, or is it variable over time requiring serial samples to measure an individual’s fluctuation over time. Lastly, what can I do about it if I am epigenetically older. Can it be reversed? Can I be rejuvenated and turn back time?

Dr Flanagan is an Editorial Board member and the author of the paper Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis published in Clinical Epigenetics.