TY - JOUR
T1 - Elevated serum levels of sCD30 and IL6 and detectable il10 precede classical hodgkin lymphoma diagnosis
AU - Levin, Lynn I.
AU - Breen, Elizabeth C.
AU - Birmann, Brenda M.
AU - Batista, Julie L.
AU - Magpantay, Larry I.
AU - Li, Yuanzhang
AU - Ambinder, Richard F.
AU - Mueller, Nancy E.
AU - Martínez-Maza, Otoniel
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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; IL6OR4.6;95%CI, 2.9-7.5] and >1 year to 2 years precHL 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.
AB - 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; IL6OR4.6;95%CI, 2.9-7.5] and >1 year to 2 years precHL 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.
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U2 - 10.1158/1055-9965.EPI-16-1012
DO - 10.1158/1055-9965.EPI-16-1012
M3 - Article
C2 - 28341757
AN - SCOPUS:85022336013
VL - 26
SP - 1114
EP - 1123
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 7
ER -