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Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene
M A Smith1, R Simon, H D Strickler
1National Cancer Institute, Division of Cancer Treatment and Diagnosis, Bethesda, MD 20892, USA.
Insights
Improved hygiene, indicated by lower hepatitis A virus (HAV) infection rates, is linked to increased childhood acute lymphoblastic leukemia (ALL) incidence. This suggests reduced early-life exposure to certain agents may elevate ALL risk.
Area of Science:
- Epidemiology
- Public Health
- Pediatric Oncology
Background:
- Childhood acute lymphoblastic leukemia (ALL) incidence varies geographically and temporally, with higher rates historically in developed nations.
- Socioeconomic development, particularly hygiene conditions, influences exposure to infectious agents and may impact ALL rates.
- Hepatitis A virus (HAV) infection patterns serve as a proxy for hygiene standards due to its fecal-oral transmission route.
Purpose of the Study:
- To investigate the association between childhood ALL incidence and hygiene conditions, using HAV infection as an indicator.
- To analyze the temporal relationship between changes in HAV infection rates and childhood leukemia trends in the United States and Japan.
Main Methods:
- Utilized HAV infection patterns (fecal-oral transmission) to assess hygiene conditions across populations.
- Employed a catalytic model to estimate HAV force of infection and age-specific seroprevalence over time.
- Correlated temporal changes in HAV infection rates with childhood leukemia mortality and incidence data.
Main Results:
- An inverse relationship was observed between HAV infection prevalence and childhood leukemia rates.
- Declines in the HAV force of infection in the US and Japan preceded observed increases in childhood leukemia incidence.
- A model correlating changes in HAV infection rates with a putative leukemia-inducing agent accurately described temporal trends in childhood leukemia for White US children and Japanese children.
Conclusions:
- Improved public hygiene, reflected by decreased HAV infection, is associated with increased childhood ALL incidence.
- The findings support a hypothesis where reduced childhood exposure to hygiene-associated infectious agents elevates ALL risk.
- Potential mechanisms include increased in utero transmission or higher rates of infant infection due to lack of maternal antibodies.
Objectives:
The incidence of acute lymphoblastic leukemia (ALL) in children has shown temporal and geographic variation during the 20th century, with higher rates in developed nations appearing in the first half of the century, but with persisting low rates in developing nations. We sought to assess the relation of childhood ALL with hygiene conditions, an aspect of socioeconomic development affecting rates of exposure to infectious agents.
Methods:
Infection patterns for hepatitis A virus (HAV), an agent with a fecal-oral route of transmission, were used to indicate hygiene conditions in different populations, with emphasis on instructive United States and Japanese data. A catalytic model was fit to these data, estimating the HAV force of infection and age-specific seroprevalence rates over time. These analyses were used to assess the temporal relationship of changes in HAV infection rates to changes in childhood leukemia mortality and incidence rates.
Results:
We observed an inverse relationship between HAV infection prevalence and rates of childhood leukemia. Further, decreases in the HAV force of infection in the United States and Japan appear to have preceded increases in childhood leukemia rates. We describe a model based on a putative leukemia-inducing agent with a change in infection rate over time correlated with that of HAV that describes well the temporal trends in childhood leukemia rates for White children in the US and for Japanese children.
Conclusion:
The data suggest that improved public hygiene conditions, as measured by decreased prevalence of HAV infection, are associated with higher childhood ALL incidence rates. The model that we present supports the plausibility of the hypothesis that decreased childhood exposure to a leukemia-inducing agent associated with hygiene conditions leads to higher rates of ALL in children by increasing the frequency of in utero transmission caused by primary infection during pregnancy (or by increasing the number of individuals infected in early infancy because of lack of protective maternal antibodies).