Understanding the interplay between early life factors, the genome and childhood cancer risk

The causes of childhood cancer are still largely unknown. Dr Natália Spitz Toledo Dias and her team will investigate whether environmental exposures during a baby’s life in the womb can cause changes to gene activity that may be associated with childhood cancer risk. The ultimate aim is to provide an evidence base for cancer prevention and discover the cancer’s molecular origins which could serve for targeted therapy.

Dr Spitz Toledo Dias’ research is funded by Children with Cancer UK under a Postdoctoral Fellowship scheme with the International Agency for Research on Cancer (IARC), which is part of the World Health Organisation (WHO). This scheme is provided to develop and support future leaders in cancer research.

Project Details

  • Project Title

    Identifying epigenetic biomarkers of early-life factors in association with childhood cancer risk.

  • Lead Researcher

    Dr Natália Spitz Toledo Dias

  • Research Centre

    International Agency for Research on Cancer (IARC), part of the World Health Organisation (WHO)

  • City & Institution Postcode

    Lyon, France, 69008

  • Start Date

    9 January 2021

  • Duration

    24 months

  • Grant Amount

    €90,000

Dr Natalia Spitz Toledo Dias

Overview

Cancer is the greatest cause of death in children in the UK, and its incidence is increasing worldwide. While a foetus is growing into a baby the womb, it is very sensitive to environmental exposures that may affect its health later in life. While important advances have been made in the diagnosis and treatment of childhood cancer, the treatment of this disease often causes major health problems for cancer survivors months or years after successful treatment. There is evidence that genetic and other molecular abnormalities may be present at birth and that factors in foetal life may be influential to the development of diseases later on.

In healthy human cells, genes can be “switched on” or “switched off” over time depending upon their job. Making sure that the right genes are switched on or off at the right time is essential for normal cell functioning. It’s increasingly understood that many diseases are caused by or associated with genes behaving incorrectly, and that some changes to gene activity can be triggered by environmental exposures. Proper regulation of gene activity is particularly crucial for a foetus to grow into a healthy baby.

Several environmental exposures in the womb and early childhood have been associated with the switching off of certain genes via an epigenetic process called “methylation”, which has then been implicated in the causes of some childhood cancers. The epigenome intricately knits the DNA strands into a molecular imprint of nature and nurture without affecting the genetic sequence itself. Epigenetic changes are heritable, affect gene activity and shape the different cells and organs, but unlike genetic mutations, epigenetic alterations are potentially reversible, hence, offering interesting targets for disease prevention. It is possible that gene methylation may act as a mediator between environment and disease outcome, and/or as a secondary event in the multiple hit pathway to developing childhood cancer.

Dr Natália Spitz Toledo Dias and her team will analyse the data of a large international childhood cohort, with the aim of understanding the underlying molecular causes of childhood cancer. They will achieve this by investigating whether changes to gene activity through methylation are driven by certain risk factors. The research will focus on exposure to pesticides during the fellowship timeframe but may include other environmental exposures of interest. This will enable them to identify key signatures of methylation that could identify a child’s risk of developing cancer. Identifying which children are at greater risk of developing cancer could help doctors to detect the disease earlier in patients. Some of these signatures may also play a driver role in cancer development and could be, hence, exploited in targeted therapy.

Potential impact

This project focuses on the early-life period, when the impact of health risk factors on developmental processes is particularly important, with potentially lifelong consequences. This study should improve our knowledge of the mechanistic causes of childhood cancer, thus, providing an evidence base for cancer prevention and targeted therapy. Dr Spitz Toledo Dias and her team expect to identify gene activity patterns associated with specific environmental exposures that are themselves associated with childhood cancer risk. Such changes to gene activity can leave key signatures and clues in patients that could be used in cancer prevention measures as well as acts as a potential target for personalised therapy.

Video: Researching the origins of childhood cancer

The International Agency for Research on Cancer (IARC) presents a new video explaining how our researchers “time-travel” to investigate the origins of childhood cancers. More children die from childhood cancers than from any other disease. Understanding what causes these cancers is key to preventing them and to finding cures.

About the research team

Dr Spitz Toledo Dias’ research is funded by Children with Cancer UK under a Postdoctoral Fellowship scheme with the International Agency for Research on Cancer (IARC), which is part of the World Health Organisation (WHO). This scheme is provided to develop and support future leaders in cancer research.

Dr Spitz Toledo Dias is based in the Epigenomics and Mechanisms (EGM) Branch (headed by Dr Zdenko Herceg) at IARC. The EGM branch’s innovative research uses a combination of genetic, population and translational studies to identify the causal links between environmental factors, gene activity and cancer and to identify and validate cancer signatures for risk stratification.