title: An infectious aetiology for childhood acute leukaemia: a review of the evidence.
abstract: There are three current hypotheses concerning infectious mechanisms in the aetiology of childhood leukaemia: exposure in utero or around the time of birth, delayed exposure beyond the first year of life to common infections and unusual population mixing. No specific virus has been definitively linked with childhood leukaemia and there is no evidence to date of viral genomic inclusions within leukaemic cells. The case-control and cohort studies have revealed equivocal results. Maternal infection during pregnancy has been linked with increased risk whilst breast feeding and day care attendance in the first year of life appear to be protective. There is inconclusive evidence from studies on early childhood infectious exposures, vaccination and social mixing. Some supportive evidence for an infectious aetiology is provided by the findings of space-time clustering and seasonal variation. Spatial clustering suggests that higher incidence is confined to specific areas with increased levels of population mixing, particularly in previously isolated populations. Ecological studies have also shown excess incidence with higher population mixing. The marked childhood peak in resource-rich countries and an increased incidence of the childhood peak in acute lymphoblastic leukaemia (ALL) (occurring at ages 2-6 years predominantly with precursor B-cell ALL) is supportive of the concept that reduced early infection may play a role. Genetically determined individual response to infection may be critical in the proliferation of preleukaemic clones as evidenced by the human leucocyte antigen class II polymorphic variant association with precursor B-cell and T-cell ALL.
authors.affiliation: Cancer Research UK Paediatric and Familial Cancer Research Group, Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, UK. richard.mcnally@man.ac.uk
authors.forename: Richard J Q
authors.initials: RJ
authors.lastname: McNally
authors.forename: Tim O B
authors.initials: TO
authors.lastname: Eden
mesh_terms: D001942:Breast Feeding; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007107:Immune System / Q000502:physiology; D010290:Parents; D011157:Population Dynamics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012931:Social Environment; D014611:Vaccination