Applying molecular epidemiology in pediatric leukemia

J Investig Med. 2016 Feb;64(2):355-60. doi: 10.1097/JIM.0000000000000204. Epub 2016 Jan 11.


Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.

Keywords: DNA repair; acute lymphoblastic leukemia; cancer predisposition; childhood leukemia; familial leukemia; genetic instability; genome wide association study; inherited cancer syndrome; inherited leukemia; molecular epidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genomic Instability
  • Humans
  • Inheritance Patterns / genetics
  • Leukemia / epidemiology*
  • Leukemia / genetics*
  • Molecular Epidemiology*