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Non-Hodgkin Lymphoma
Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies
Mara M. Epstein,1 Bernard Rosner,2,3 Elizabeth C. Breen,4,5 Julie L. Batista,3 Edward L. Giovannucci,3,6,7 Larry Magpantay,4,8 Jon C. Aster,9 Scott J. Rodig,9 Kimberly A. Bertrand,10 Francine Laden,3,7 Otoniel Martínez-Maza4,8,11,12,13 and Brenda M. Birmann3
1Department of Medicine and the Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, MA; 2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA; 3Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; 4UCLA AIDS Institute, Los Angeles, CA; 5Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA; 6Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; 7Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; 8Department of Obstetrics & Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA; 9Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; 10Slone Epidemiology Center at Boston University, Boston, MA; 11Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA; 12Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA and 13Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
ABSTRACT
Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker pro- files associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses’ Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune mark- er levels with multiplexed immunoassays. Using multivariable logistic regression we calculated Odds Ratios (OR) and 95% Confidence Intervals (CI) per standard deviation unit increase in biomarker concen- tration for risk of non-Hodgkin lymphoma and major histological sub- type, stratifying additional models by years (<5, 5 to <10, ≥10) after blood draw. Soluble interleukin-2 receptor-α, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individ- ually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lym- phoma and one or more subtypes. The biomarker combinations associ- ated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (OR: 95%CI: 0.51, 0.43-0.62) persisted more than ten years after blood draw (OR: 0.70; 95%CI: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diag- nosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis.
Introduction
Severe immune compromise is a strong risk factor for non-Hodgkin lymphoma (NHL), and B-cell activation and inflammation have been associated with an increased risk of AIDS-related NHL. Elevated pre-diagnosis plasma levels of mark- ers of B-cell stimulation including CXC chemokine ligand 13 (CXCL13; a B-cell attracting chemokine),1 interleukin (IL)-6 (a B-cell stimulatory cytokine), and solu- ble (s) CD30 (sCD30; a soluble receptor indicative of B- and T-cell activation) pre-
Ferrata Storti Foundation
Haematologica 2018 Volume 103(10):1679-1687
Correspondence:
brenda.birmann@channing.harvard.edu
Received: November 7, 2017. Accepted: June 15, 2018. Pre-published: June 21, 2018.
doi:10.3324/haematol.2017.183236
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/10/1679
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