DNA Methylation as a Potential Mediator of Environmental Risks in the Development of Childhood Acute Lymphoblastic Leukemia

Abstract

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development.

Keywords::

• acute lymphoblastic leukemia
• alcohol
• birth weight
• caffeine
• developmental programming
• DNA methylation
• environment
• folate
• iron
• smoking

Financial & competing interests disclosure

Funding was provided via a studentship from the Institute of Health and Society, Newcastle University, UK, and from the North of England Children’s Cancer Research charity (NECCR). CL Relton is supported by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_12013_2) and Cancer Research UK (C18281/A19169). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Funding was provided via a studentship from the Institute of Health and Society, Newcastle University, UK, and from the North of England Children’s Cancer Research charity (NECCR). CL Relton is supported by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_12013_2) and Cancer Research UK (C18281/A19169). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.