Epidemiology Program

Markers of B-Cell Stimulation as Potential Predictors of Non-Hodgkin Lymphoma

PI: Anneclaire De Roos, PhD

There is intriguing evidence that markers of B-cell stimulation may be implicated in development of B-cell NHL, from studies among immunocompromised patient populations, however, such factors have been little studied in the general (primarily immunocompetent) population.  We are conducting a nested case-control study of biologic markers of a B-cell stimulatory host environment as predictors of B-cell NHL among 500 cases and 500 pair-matched controls from the WHI Observational Study (OS), among whom biologic samples were collected an average of 10 years before NHL diagnosis.  Our primary aims are to: 1) Evaluate the risk of B-cell NHL associated with immune parameters, measured in prediagnostic plasma/serum, that are indicative of a B-cell stimulatory host environment, including levels of certain cytokines (e.g., IL6, IL10, TNFα), cytokine-like molecules (sCD23), soluble cytokine receptors (sCD27, sCD30), and other molecules involved in B-cell response (sCD44, CXCL13); 2) Measure EBV DNA load and antibodies to key EBV antigens (VCA, EBNA1, and EA-D), for estimation of the risk of B-cell NHL associated with EBV, a cause of B-cell proliferation; and 3) Investigate whether observed associations differ by major NHL subtype, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma.  We will also describe the patterns of association according to the number of years between blood sample collection and NHL diagnosis, in order to inform our interpretation of marker-NHL associations as potentially etiologic or as a reflection of early NHL pathogenesis.