Infectious Etiology

Specific viruses can cause leukemia in animals (feline leukemia virus, bovine leukemia virus), and the human T-cell lym-photropic virus type 1 (HTLV-1) retrovirus is associated with the development of a rare type of adult leukemia (T cell). Although there is currently no biological evidence that viruses play a role in childhood leukemia, there are several intriguing hypotheses based on observations and associations that merit further research.14,15,63 Two major hypotheses with respect to infectious exposures and childhood leukemia attempt to explain the age peak of ALL in children 2 to 5 years of age.14,15 The first theory suggests a two-hit model of leukemogenesis: The first event occurs in utero when immature B cells are rapidly dividing; the second genetic event occurs in the first few years of life, and is strongly influenced by the timing of exposure to infectious agents.14 In contrast, the second theory suggests that childhood leukemia is a rare response to direct viral exposures and that leukemia clusters occur when herd immunity is deregulated by population mixing.15 Although there have been some indirect studies (cluster, ecological) that provide some support to the latter hypothesis, these associations could also be explained by other factors including chance.64,65 Findings from recent case-control studies that have investigated patterns of infection and access to day care, which may be a surrogate indicator of the timing of exposure to infectious agents, have been inconsistent; one small study reported an association with timing of day care, where early day care conferred a modest protective effect.66 However, a recent study of over 1800 cases of childhood ALL found no association with the timing of day care.67

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