Investigation of Epstein-Barr Virus as a Potential Cause of B-Cell Non-Hodgkin Lymphoma in a Prospective Cohort
Menée à partir d'échantillons sanguins prélevés sur 491 patientes atteintes d'un lymphome non hodgkinien à cellules B et sur 491 témoins, cette étude prospective de cohorte analyse l'association entre une infection par le virus d'Epstein-Barr et le risque de développer la maladie
Background : We hypothesized that poor control of Epstein-Barr virus (EBV) infection, leading to reactivation of the virus, increases the risk of non-Hodgkin lymphoma (NHL) in the general population of primarily immunocompetent persons. Methods : We conducted a case-control study nested within the Women's Health Initiative Observational Study cohort in which we measured antibodies to EBV antigens (IgG to viral capsid antigen [VCA], nuclear antigen [EBNA1], and early antigen [EA-D]) and EBV DNA load in prediagnostic samples of 491 B-cell NHL cases and 491 controls. Results : We found no association with established EBV infection, based on seropositivity for VCA. Seropositivity for EBNA1 was associated with decreased risk of B-cell NHL, overall (odds ratio [OR]=0.5, 95% confidence interval [CI]: 0.3-0.8) and for each of the histologic subtypes examined. Increased risk of chronic lymphocytic leukemia (CLL) and related subtypes was observed with higher levels of EBV DNA and antibody to EA-D, both markers reflective of reactivation. These associations were strongest for cases with the shortest time interval between blood draw and diagnosis. Conclusions : In balance, these results do not provide strong evidence of EBV playing a causal role in B-cell NHL in general population women. The associations we observed may reflect increased risk of NHL with underlying immune impairment or could be due to reverse causation. Impact: Further characterization of the subtype-specific association with CLL is warranted. Exclusion of cases with preclinical disease markers (such as monoclonal B-lymphocytosis for CLL) may help rule out reverse causation in future studies.