A Population-Based Nested Case-Control Study of Prediagnostic Serum Antibodies to JC Virus and BK Virus and Risk of Non-Hodgkin’S Lymphoma.

Viral infections such as HIV, EBV, and HCV have been associated with increased risk of non-Hodgkin’s lymphoma (NHL). We conducted a nested case-control study to investigate the association between prediagnostic serum antibodies to JC virus (JCV) and BK virus (BKV) and subsequent risk of NHL. Methods: Two research serum banks were established in Washington County, MD, with more than 45,000 volunteers contributing blood samples collected in 1974 and 1989. Incident cases of NHL diagnosed through 2002 (n=170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n=340) on age, sex, and date of blood draw. Pre-diagnostic circulating IgG antibodies to JCV and BKV were measured using virus-like particle (VLP) enzyme-linked immunosorbant assays (ELISA). Associations between JCV and BKV antibody seropositivity and NHL were estimated using conditional logistic regression. Results: Overall, neither serum antibodies to JCV (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.56–1.23) or BKV (OR = 0.98, 95% CI = 0.64–1.48) were associated with an increased risk of NHL. Results were similar across NHL subtypes. Examining time to diagnosis suggested a possible increase in NHL risk associated with JCV antibodies, but not BKV antibodies, among individuals diagnosed 12–20 years after the time of blood draw. Among a subset of individuals who donated blood in both 1974 and 1989, those who experienced an increase in JCV antibody levels over time were more than four times as likely to develop NHL as compared to those whose antibody levels steeply declined (OR = 4.59, 95% CI = 1.30–16.25). Conclusion: The finding of increased risk with increasing JCV antibody titers suggests a possible association between reactivation of JCV infection and subsequent NHL.