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Enterovirus infections may reduce risk for leukemia in children
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Children infected with enterovirus faced a reduced risk for developing leukemia, according to the results of a retrospective cohort study.
The results of the analysis support a delayed infection hypothesis for the cause of childhood leukemia, according to the researchers.
“Leukemia is the most common cancer in children, accounting for more than a third of childhood malignancies,” Chia-Hung Kao, MD, of the Graduate Institute of Clinical Medical Science at China Medical University in Taiwan, and colleagues wrote. “Greaves proposed the delayed infection hypothesis in childhood leukemia [Greaves MF. Leukemia. 1988;2:120-25]. According to this hypothesis, children who have a delayed exposure to common infections have a more vigorous immune response.”
Enteroviruses — which include over 90 distinct viral serotypes — are common in children, occurring in 10 million to 15 million children in the U.S. per year. However, the association between enterovirus infection and risk for leukemia remains unclear, according to study background.
Kao and colleagues conducted a nationwide retrospective cohort study to assess the risk for leukemia following enterovirus infection. They accessed records from the National Health Insurance Research Database in Taiwan to identify children with enterovirus infections aged younger than 18 years. They then randomly selected and frequency-matched children with enterovirus infections with uninfected children by age, sex, urbanization level, parental occupation and index year.
The researchers only included children with complete age and sex baseline data and at least three clinic visits.
Diagnosis of leukemia during follow-up served as the primary endpoint.
From approximately 3.05 million randomly selected insurance claims, the researchers identified 282,360 children infected with enterovirus and 282,355 children not infected with enterovirus between January 2000 and December 2007.
Children with enterovirus infections had a leukemia incidence density rate of 3.26 per 100,000 person-years, whereas children without enterovirus infections had a leukemia incidence density rate of 5.84 per 100,000 person-years.
Children with enterovirus infections faced a significantly lower risk for developing leukemia when compared with non-infected children (adjusted subhazard ratio [SHR] = 0.44; 95% CI, 0.31-0.6).
Further, children with enterovirus infections exhibited a reduced risk specifically for acute lymphoblastic leukemia (adjusted SHR = 0.44; 95% CI, 0.3-0.65) and acute myeloid leukemia (adjusted SHR = 0.4; 95% CI, 0.17-0.97).
The main diseases associated with the reduced risk for leukemia included hand-foot-and-mouth disease (P = 0.3) and herpangina (P = .0003).
The researchers acknowledged several study limitations, including the inability to include several risk factors for childhood leukemia, such as air pollution, exposure to pesticides and tobacco smoking. Further, they did not have access to information regarding T-cell or B-cell ALL.
“To our knowledge, no similar investigation has examined the association of enterovirus infection with leukemia in the scientific literature,” Kao and colleagues wrote. “This large nationwide retrospective cohort study showed a reduced risk [for] leukemia in children with enteroviruses, particularly in those who had no allergic diseases. Additional investigations are needed to unravel the pathogenesis of enterovirus infections and childhood leukemia.”
Though promising, the results of this study require further validation, Logan G. Spector, PhD, professor of pediatric epidemiology at University of Minnesota Medical School, wrote in an accompanying editorial.
“In view of the general absence of strong, modifiable risk factors for childhood leukemia, this study is exciting because it alludes to the possibility of inoculation against the most frequent forms of cancers in children,” Spector wrote. “Yet, a crisis of reproducibility exists in biomedical science, perhaps even more acute in observational research, and so the first priority should be to attempt replication of these findings in other datasets. This study presents a solid foundation on which to build conclusions.” – by Cameron Kelsall
Disclosure: The researchers and Spector report no relevant financial disclosures.
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