Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis.
Background:We investigated whether an immune system environment characterized by elevated serum levels of B-cell activation molecules was associated with the subsequent development of classical Hodgkin lymphoma (cHL).Methods:We measured serum levels of B-cell-stimulatory cytokines, IL6 and IL10, soluble CD30 (sCD30), and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Serum Repository.Results:Prediagnosis serum sCD30 and IL6 levels had strong positive associations with risk of a cHL diagnosis 0 to 1 year prior to diagnosis [sCD30 OR = 5.5; 95% confidence interval (CI), 3.4-9.0; IL6 OR = 4.6; 95% CI, 2.9-7.5] and >1 year to 2 years pre-cHL diagnosis (sCD30 OR = 3.3; 95% CI, 1.6-6.7; IL6 OR = 2.9; 95% CI, 1.3-6.5). We observed similar, albeit not consistently significant positive associations, over 4 or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL10 levels were significantly associated with Epstein-Barr virus (EBV)-positive cHL cases compared with EBV-negative cases.Conclusion:In this prospective analysis, elevated sCD30 and IL6 levels and detectable IL10 preceded cHL diagnosis.Impact:The associations of these cytokines with cHL risk may reflect the production of these molecules by proliferating nascent cHL tumor cells, or by immune cells responding to their presence, prior to clinical detection. The stable elevation in cHL risk, 4 or more years prediagnosis, also suggests that a B-cell-stimulatory immune system milieu precedes, and may promote, lymphomagenesis.Cancer Epidemiol Biomarkers Prev; 26(7); 1114-23. ©2017 AACR.
Department of Epidemiology, Preventive Medicine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland. lynn.i.levin.civ@mail.mil.
Lynn I
LI
Levin
Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California.
Elizabeth C
EC
Breen
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Brenda M
BM
Birmann
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Julie L
JL
Batista
Department of Obstetrics & Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California.
Larry I
LI
Magpantay
Department of Epidemiology, Preventive Medicine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland.
Yuanzhang
Y
Li
Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.
Richard F
RF
Ambinder
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Nancy E
NE
Mueller
Department of Obstetrics & Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California.|Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California.|Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California.
Otoniel
O
Martínez-Maza
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D063646:Carcinogenesis / Q000276:immunology; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D017730:Ki-1 Antigen / Q000097:blood* / Q000276:immunology; D008297:Male; D008889:Military Personnel / Q000706:statistics & numerical data; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States; D059030:United States Department of Defense; D055815:Young Adult
C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D017730:Ki-1 Antigen; D016753:Interleukin-10; D007073:Immunoglobulin E