Cindy Chang

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NCI, DCEG, IIB

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PLCO (Learn more about this study)

2010-0135

Sep 23, 2010

GBV-C INFECTION AND RISK OF NHL IN THE PLCO COHORT

Non-Hodgkin lymphoma (NHL) is the 6th most common cancer in U.S. men and women. Known risk factors including severe immunosuppression do not account for the majority of cases. Chronic immune stimulation by infectious agents such as hepatitis C virus (HCV) is thought to play a role in the development of lymphoma. There is a growing interest in the association between GB virus type C (GBV-C) and NHL due to its similarities to HCV and its ability to replicate in B-cells. GBV-C is transmitted through blood, including transfusions and sexually, and is detected in 1-2% of healthy blood donors. A recent population-based case-control study reported a positive association (OR=2.7, 95% CI 2.1-13.7) between GBV-C RNA in serum/plasma and NHL. The next step is to confirm this association in a prospective design in order to minimize selection bias in controls, mitigate disease and treatment effects on GBV-C status, as well as to evaluate, through the use of serial samples, whether persistence of the virus leads to increased risk of NHL. If the association between GBV-C and NHL is confirmed, there may be important implications for screening blood donors.
We propose to test for active and past infection with GBV-C in baseline serum samples from 536 NHL cases and 1,072 controls (frequency-matched by age, sex, ethnicity, and time from baseline to diagnosis/selection) enrolled in the screening arm of PLCO in order to evaluate whether active or past infection with GBV-C is associated with subsequent NHL risk. Additionally, we propose to test followup serum in individuals who tested positive for GBV-C RNA to evaluate whether persistent infection increases risk of NHL. Examining the association between GBV-C and NHL in a large, prospective cohort is timely, may have important public health implications, and may help further elucidate the etiology of NHL.

To evaluate markers of GBV-C infection in NHL cases compared to controls, in a case-control study nested within PLCO.

1. We hypothesize that the prevalence of active GBV-C infection, as indicated by detection of viremia, is greater in cases compared to controls. To carry out this aim, we propose to test baseline serum samples from all study participants for GBV-C RNA using RT-PCR.

2. We hypothesize that individuals with persistent GBV-C infection are at greater risk of NHL compared to individuals with cleared infection. To carry out this aim, we propose to test follow-up serum samples only from study participants testing positive at baseline for GBV-C RNA using RT-PCR.

3. We hypothesize that the prevalence of past GBV-C infection is greater in cases than in controls. To carry out this aim, we propose to test all baseline serum samples from study participants for antibodies to GBV-C E2 protein using ELISA.