Longitudinal tracking of genetic and epigenetic signals for blood-cancer risk prediction

Principal Investigators: Dr Jamie Blundell, University of Cambridge; Dr Hisham Mohammed, Oregon Health and Science University and Dr Ruth Etzioni, Oregon Health and Science University

Funded by: CRUK-OHSU Early Detection Joint Project Award 2020

The first genetic and epigenetic steps towards cancer occur in healthy tissue decades before cancer onset. This raises the possibility that these early events could be used as a bellwether for predicting who is most at risk of developing cancer. Serial blood samples collected annually from hundreds of thousands of initially healthy people in the UKCTOCS study afford a unique opportunity to do this. By 'zooming in' on the people who subsequently develop cancer, we can 'rewind' time by performing genetic and epigenetic analyses on blood samples collected years before the cancer was diagnosed.

An attractive initial target for this ambitious vision is the aggressive blood cancer Acute Myeloid Leukaemia (AML). Because AML is characterised by a relatively small number of genetic and epigenetic alterations, which are readily detectable in peripheral blood, it provides a unique opportunity to address one of the most fundamental questions in early detection: “How many years before diagnosis can cancer be reliably predicted?” Our principle aim in this project is to perform a range of methylation sequencing on pre-AML samples to paint a quantitative epigenetic portrait of how AML evolves from healthy tissue and use these data to develop statistical techniques to forecast blood-cancer risk.