UC San Diego

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 [immunoglobulin G (IgG) to viral capsid antigen (VCA), nuclear antigen (EBNA1), and early antigen-diffuse (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 [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.