Delayed exposure to infections and childhood lymphomas: a case-control study

Delayed exposure to common infections during childhood, have been implied to cause strong immunological response to a single infectious agent that eventually triggers leukemogenesis. The aim of the present study was to investigate whether decreased exposure to infections, as reflected in a more seronegative spectrum to several common infectious agents, is associated with increased risk for the development of childhood lymphomas. All 125 children (up to 14 years old), with Hodgkin (HL, n = 52) and non-Hodgkin lymphomas (NHL, n = 73) diagnosed through the national network of childhood Hematology-Oncology units during an 8-year period were enrolled in the study along with 125 age- and gender-matched controls. Past exposure to nine common infections [respiratory syncytial virus (RSV), influenza A and B, parainfluenza type 1, adenovirus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV6), Bartonella henselae] was assessed using serological markers. After controlling for possible confounding factors, the overall seronegativity status upon diagnosis was statistically significantly associated with NHL [odds ratio; 95% CI: 1.45 (1.10-1.93), p = 0.01] and less so with HL risk [odds ratio; 95% CI: 1.30 (0.83-2.05), p = 0.25]. A statistically significant association of seronegativity with the development of NHL was evident for RSV [odds ratio; 95% CI: 7.27 (1.59-33.28), p = 0.01], EBV [odds ratio; 95% CI: 6.73 (1.45-31.20), p = 0.01] and suggestive association for influenza B [odds ratio; 95% CI: 2.60 (0.90-7.55), p = 0.08] and influenza A [odds ratio; 95% CI: 2.35 (0.81-6.80), p = 0.11]. In contrast, there was no evidence for association of HL with negative serology for any of the infectious agents tested. The risk of lymphomas, especially NHL, might be higher when, due to lower exposure to several infectious agents, the relatively unmodulated immune system of a child is challenged by environmental stimuli that can trigger development of lymphomas. The results, however, need further confirmation, through more pertinent methodological designs.