EB SYMPOSIUM MANUSCRIPT Applying Molecular Epidemiology in Pediatric Leukemia

to d ia ic st s, e as w n us of y ic id e ry yAbstract: Molecular epidemiology is the study of genetic and enviro mental risk for disease, with much effort centered on cancer. Childhoo leukemia occurs in nearly a third of all patients newly diagnosed with p diatric cancer. Only a small percentage of these new cases of childhood le kemia are associated with high penetrant hereditary cancer syndrome Childhood leukemia, especially acute lymphoblastic leukemia, has be associated with a dysregulated immune system due to delayed infectio exposure at a young age. Identical twins with childhood leukemia sugge that acute lymphoblastic leukemia begins in utero and that the concorda presentation is due to a shared preleukemia subclone via placental transf Investigation of single nucleotide polymorphisms within candidate gen find that leukemia risk may be attributed to population-based polymo phisms affecting folate metabolism, xenobiotic metabolism, DNA repa immunity, and B-cell development. More recently, genome-wide associ tion studies for leukemia risk has led investigators to genes associated wi B-cell development. When describing leukemia predisposition due to h reditary cancer syndromes, the following 6 categories become appare on the basis of biology and clinical presentation: (1) genetic instabilit DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bo marrow failure syndromes, (4) telomere maintenance syndromes, (5) im munodeficiency syndromes, and (6) transcription factor syndromes an pure familial leukemia. Understanding the molecular epidemiology childhood leukemia can affect the treatment and tumor surveillance strat gies for these high risk patients and their family members.