Approved Research

Investigation of altered DNA methylation, induced by anti-cancer therapies, as a mediating mechanism of serious late health effects in survivors of childhood/young adult cancer

Lay summary

Survival in childhood cancer is generally good. However, many childhood cancer survivors experience severe health problems in later life; including significantly increased development of aging-associated diseases at a young age and excess in early deaths, with second cancers and heart disease the main causes. Health in cancer survivors is an increasingly important medical issue in the UK, with estimates suggesting there will be 4-million cancer survivors in the UK by 2030. This project will investigate a potential cause of these late health effects; DNA methylation. DNA methylation is a covalent change that occurs in our DNA. Importantly, when exposure to toxic substances changes DNA methylation in humans, these changes are generally stable and will be maintained many years after exposure to the toxic substance has ceased.

We have previously shown that significant alterations in DNA methylation are induced by anti-cancer treatments in children. Because these DNA methylation changes are usually stably maintained, we hypothesise that alterations induced by anti-cancer therapies will be maintained life-long and thus will be able to impact the individual's health many years after therapy has ceased. We are now determining which methylation changes induced by anti-cancer therapies are still present in adult survivors who were treated for childhood/young adult cancer and gathering information to allow subsequent studies to determine the extent to which these DNA methylation changes predict which health problems survivors will suffer from.  After we have achieved this, we hope that assessing DNA methylation changes in childhood cancer survivors could be used to direct (and improve) follow-up care for survivors and also help design new treatment approaches to reduce/eliminate adverse late health effects.