title: Epidemiology of childhood leukemia in the presence and absence of Down syndrome.
abstract: Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.
authors.affiliation: Exponent Health Sciences, 149 Commonwealth Drive, Menlo Park, CA 94025, United States. Electronic address: gmezei@exponent.com.
authors.forename: Gabor
authors.initials: G
authors.lastname: Mezei
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA 90095, United States.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Sudan
authors.affiliation: Sheba Medical Center Tel-Hashomer, Ramat Gan 52621, Israel; Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA 90095, United States.
authors.forename: Leeka
authors.initials: L
authors.lastname: Kheifets
mesh_terms: D002648:Child; D004314:Down Syndrome / Q000453:epidemiology* / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology; D012307:Risk Factors
keywords: Acute leukemia; Childhood leukemia; Children; Down syndrome; Etiology