Mark Purdue

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NCI, DCEG, OEEB

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PLCO (Learn more about this study)

2010-0145

Sep 23, 2010

A prospective study of immunologic markers and risk of lymphoid malignancies

There is abundant epidemiologic evidence that severe immune dysregulation increases the risk of lymphoid malignancies (LM) such as non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), and growing evidence suggests that immunologic factors & conditions in immunocompetent people are also associated with increased risks of these neoplasms. Associations between immunologic responses and risk of LM are suspected to be mediated in part through the effects of cytokines, chemokines and other molecules secreted by immune cells. Measurements of these molecules in plasma within epidemiologic studies may provide important insight into the disease process at the tissue level. In a previous NHL study within PLCO involving nine immune markers, we uncovered associations with sCD27 and sCD30, markers for T-cell and B-cell activation, respectively. To extend our investigations of immune markers and lymphoma risk within PLCO, we propose to conduct a nested case-control study of LM (570 cases, 570 controls) investigating plasma levels of at least 60 immunologic markers, to be measured using Luminex-based multiplex assay panels at SAIC-Frederick. A maximum of 400ul of heparin plasma (including dead volume) is requested for these assays. Associations between analyte levels and LM, both overall and by major LM subtype, will be computed using conditional and polytomous regression modeling, respectively. For comparisons between the highest and lowest tertile of any given biomarker, the study will have greater than or equal to 80% power to detect an OR for LM of 1.50, and ORs for NHL and MM of 1.55 and 2.10 respectively. This research project has significant implications for improving our understanding of the role of immune system modulation in the etiology of LM.