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, interleukin (IL)-6 and IL-10, soluble CD30 (sCD30) and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Department of Defense Serum Repository. Results:Pre-diagnosis serum sCD30 and IL-6 levels had strong positive associations with risk of a cHL diagnosis 0-1 year prior to diagnosis (sCD30 odds ratio [OR] =5.5, 95% confidence interval [CI] = 3.4-9.0; IL-6 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; IL-6 OR = 2.9, 95% CI = 1.3-6.5). We observed similar, albeit not consistently significant positive associations, over four or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL-10 levels were significantly associated with Epstein-Barr virus (EBV)-positive cHL cases compared with EBV-negative cases. Conclusions:In this prospective analysis, elevated sCD30 and IL-6 levels and detectable IL-10 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, four or more years pre-diagnosis, also suggests that a B cell-stimulatory immune system milieu precedes, and may promote, lymphomagenesis.
- Received December 12, 2016.
- Revision received March 9, 2017.
- Accepted March 10, 2017.
- Copyright ©2017, American Association for Cancer Research.