Abstract 685: Circulating immune markers and risks of non-Hodgkin lymphoma subtypes: A pooled analysis
Authors: Rhee Jongeun , Birmann Brenda M. , De Roos Anneclaire J. , Epstein Mara M. , Martinez-Maza Otoniel , Breen Elizabeth C. , Levin Lynn I. , Visvanathan Kala , Hosgood H Dean , Rohan Thomas , Qi Lihong , Lan Qing , Rothman Nathaniel , Purdue Mark P. 
Published: June 2022

Abstract
Background: Peripheral blood levels of soluble CD27 (sCD27), sCD30 and chemokine ligand-13 (CXCL13) are proposed markers of immune activation, the effects of which may influence the development of non-Hodgkin lymphoma (NHL). Pre-diagnostic circulating levels of sCD27, sCD30 and CXCL13 have been associated with NHL, although individual studies have typically been underpowered to assess associations for individual NHL subtypes. We pooled data from eight case-control studies nested within general-population cohorts to investigate subtype-specific relationships with these immune markers.
Methods: After pooling, immune marker data for 2,455 cases diagnosed &gt;2 years after blood collection and 3,310 controls were available for analysis. Using polytomous regression models, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study-specific tertiles of each immune marker to the following subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n=623), diffuse large B-cell lymphoma (DLBCL; n=621), follicular lymphoma (FL; n=398), marginal zone lymphoma (MZL; n=138), mantle cell lymphoma (MCL; n=82) and T-cell lymphoma (TCL; n=92).
Results: We observed associations with DLBCL for elevated levels of sCD27 [OR for 3rd vs. 1st tertile (ORT3) = 2.2, 95% CI = 1.6-3.1; Ptrend = 9.3x10-6), sCD30 (ORT3 = 2.0, 95% CI 1.6-2.5; Ptrend = 6.5 x10-10) and CXCL-13 (ORT3 = 2.3, 95% CI 1.8-3.0; Ptrend = 3.9 x10-12). These associations remained in a model simultaneously adjusting for all three markers. We also observed associations with sCD27 for CLL/SLL (ORT3 = 3.3, 95% CI = 2.4-4.6; Ptrend = 1.6x10-13), MZL (ORT3 =7.7, 95% CI 3.0-20.1; Ptrend = 2.3x10-6) and TCL (ORT3 = 3.4, 95% CI 1.5-7.7; Ptrend = 0.003), and between sCD30 and FL (ORT3 = 2.7, 95% CI 2.0-3.5; Ptrend = 1.7x10-12), all of which remained after adjustment for the other immune markers. In analyses stratified by follow-up time from blood collection to case diagnosis, the sCD27-TCL association and all three DLBCL associations were equivalent across both follow-up periods (&gt;2-&lt;7.5, ≥7.5 years). The sCD27-CLL/SLL, sCD27-MZL and sCD30-FL associations were weaker for cases diagnosed ≥7.5 years post-phlebotomy compared to the earlier follow-up period but remained statistically significant. Conclusions: In this pooled analysis, to our knowledge the first of its kind, we found robust evidence of an association between the three immune markers and DLBCL, consistent with hypotheses that mechanisms related to immune activation are important in the etiology of this malignancy. Other findings are notable, particularly the strong associations with sCD27 for the rare subtypes MZL and TCL, but require further investigation before causal inferences can be drawn.
Citation Format: Jongeun Rhee, Brenda M. Birmann, Anneclaire J. De Roos, Mara M. Epstein, Otoniel Martinez-Maza, Elizabeth C. Breen, Lynn I. Levin, Kala Visvanathan, H Dean Hosgood, Thomas Rohan, Lihong Qi, Qing Lan, Nathaniel Rothman, Mark P. Purdue. Circulating immune markers and risks of non-Hodgkin lymphoma subtypes: A pooled analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 685.