Viral infections 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 the human polyomaviruses, JC (JCV) and BK (BKV), and subsequent risk of NHL. Two research serum banks were established in Washington County, Maryland, in 1974 and 1989, with the collection of blood samples from >45,000 volunteers. Incident NHL cases 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 blood draw date. Prediagnostic IgG antibodies to JCV and BKV were measured using virus-like particle ELISA. Associations between JCV and BKV antibody seropositivity and NHL were estimated using conditional logistic regression. Overall, neither antibodies to JCV [odds ratio (OR), 0.83; 95% confidence interval (95% CI), 0.56-1.23] nor BKV (OR, 0.98; 95% CI, 0.64-1.48) were associated with an increased risk of NHL. Results were similar after stratification by NHL subtype or induction period and adjustment for EBV seropositivity. Among those who donated blood in both 1974 and 1989, an increase in JCV antibody levels over time was associated with a 4-fold increased risk of NHL compared with a steep decline in antibody levels (OR, 4.59; 95% CI, 1.30-16.25; Ptrend = 0.02). Whereas JCV seropositivity was not associated with NHL overall, the finding of an increased risk of NHL associated with increasing antibody levels among those who were seropositive at baseline warrants further research into factors influencing reactivation of JCV infection.
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