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Serum Levels of Cytokines, Other Immunologic Markers and non-Hodgkin Lymphoma: A Nested Case-Control Study in the PLCO Trial

Principal Investigator
Name
Mark Purdue
Degrees
-
Institution
NCI, DCEG, OEEB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2005-0015
Initial CDAS Request Approval
Apr 21, 2006
Title
Serum Levels of Cytokines, Other Immunologic Markers and non-Hodgkin Lymphoma: A Nested Case-Control Study in the PLCO Trial
Summary
It is unclear whether immune system function influences the risk of non-Hodgkin lymphoma (NHL) in the general population. Recent findings suggest that NHL susceptibility may be influenced by single-nucleotide polymorphisms in genes (IL4, IL10, LTA, TNF) encoding cytokines, secreted proteins that modulate B- and T lymphocyte proliferation and function. These reports offer important evidence linking cytokine activity, and immune modulation, to NHL risk. However, the relationship between immunologic markers and NHL risk in the general population has not been examined. Prospective investigations incorporating direct measurements of the immune environment are needed to clarify the relevance of immunologic factors to lymphomagenesis. To address this question, we propose a nested case-control study (240 cases, 240 controls) to investigate the relationship between NHL and pre-diagnostic levels of cytokines and other relevant markers that reflect B cell activation and inflammation using T0 serum samples from the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. A panel of multiplex assays for use on the Luminex LabMAPTM system will be used to measure 12 analytes; two other analytes will be measured using ELISA. In total, 300 uL of serum will be used for these analyses, to be conducted at the University of Pittsburgh Cancer Institute Immunologic Monitoring Laboratory. The association between analyte levels and NHL will be estimated using odds ratios (OR) and 95% confidence intervals calculated from conditional logistic regression modeling. This study will have adequate power to detect moderate associations (e.g., above-median OR of 1.7 or greater, upper-quartile OR of 2.0 or greater). This research project has significant implications for improving our understanding of the role of immune modulation in the etiology of NHL, a relatively common yet poorly understood cancer. Our research will also explore whether immunologic factors hold promise as early markers of disease, an important but under-studied area of research.
Aims

The aim of our study is to investigate whether NHL risk is associated with pre-diagnostic serum levels of: 1) cytokines, both pro-inflammatory (IL-1A, IL-1B, IL-2, IL-6, IL-8, IL-12, TNFa, IFN?) and anti-inflammatory (IL-4, IL-10, IL-13); and 2) soluble markers of B cell activation (sCD23), Th2 cell activity (sCD30) and inflammation (sTNFRII). Given that chronic inflammation and increased B cell activation are mechanisms suspected to promote lymphomagenesis, we hypothesize that elevated concentrations of pro-inflammatory and B-cell stimulatory factors (IL-1A, IL-1B, IL-2, IL-6, IL-8, IL-12, TNFa, IFN?, sCD23, sCD30, sTNFRII) are associated with an increased risk of NHL. Conversely, we expect elevated concentrations of anti-inflammatory factors (IL-4, IL-10, IL-13) to be associated with decreased risk.

Collaborators

Dalsu Baris (NCI, DCEG)
Richard Hayes (NCI, DCEG)
Wen-Yi Huang (NCI, DCEG)
Lindsay Morton (NCI, DCEG)
Mark Purdue (NCI, DCEG)
Qing Lang (NCI, DCEG)
Nathaniel Rothman (NCI, DCEG)
Sonia Wang (NCI, DCEG)

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