Prevention and Epidemiology GBV-C Infection and Risk of NHL among U.S. Adults

Some retrospective studies suggest an association between infection with GB virus-C (GBV-C) and nonHodgkin lymphoma (NHL).We evaluated this association prospectively in a nested case–control study within the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases (N 1⁄4 658) and controls (N 1⁄4 1,316) were individually matched by age, sex, race/ethnicity, timing of study entry, and sample selection. Prediagnostic PLCO serum sampleswere tested for GBV-CRNA (as ameasure of active infection) and E2 antibody (active or resolved infection). Logistic regression was used to estimate odds ratios (OR) for the association between GBV-C and NHL overall and NHL subtypes. Twelve cases (1.8%) and seven controls (0.5%) were GBV-C RNA-positive. GBV-CRNApositivitywas associatedwithNHLoverall [OR, 3.43; 95% confidence interval (CI), 1.35– 8.71] and, based on small numbers, diffuse large B-cell lymphoma (OR, 5.31; 95% CI, 1.54–18.36). The association with NHL persisted when the interval between testing and selection was greater than 4 years (OR, 6.00; 95% CI, 1.21–29.73). In contrast, E2 antibody positivity was not associated with NHL risk (OR, 1.08; 95% CI, 0.74–1.58). Our study demonstrates that GBV-C infection precedes development of NHL. GBV-C infection may play an etiologic role in a small proportion of NHL cases, perhaps by causing chronic immune stimulation or impaired immunosurveillance. Cancer Res; 74(19); 1–8. 2014 AACR.