DNA methylation and the hygiene hypothesis: connecting respiratory allergy and childhood acute lymphoblastic leukemia

Abstract

Aim: The hygiene hypothesis states that a lack of infection in early-life suppresses immune system development, and is linked to respiratory allergy (RA) and childhood acute lymphoblastic leukemia (ALL) risk. Little is known about underlying mechanisms, but DNA methylation is altered in RA and ALL, and in response to infection. We investigated if aberrant methylation may be in common between these diseases and associated with infection. Materials & methods: RA and ALL disease-associated methylation signatures were compared and related to exposure-to-infection signatures. Results: A significant number of genes overlapped between RA and ALL signatures (p = 0.0019). Significant overlaps were observed between exposure-to-infection signatures and disease-associated signatures. Conclusion: DNA methylation may be a mediating mechanism through which the hygiene hypothesis is associated with RA and ALL risk.

Keywords: DNA methylation; allergy; childhood acute lymphoblastic leukemia; cold symptoms; day care; epigenetics; exposure; hygiene hypothesis; infection; proxy.