Abstract 600: Clues to understanding the association between B-activation markers and the risk of B-cell non-Hodgkin lymphoma
Authors: Teras Lauren R. , Gaudet Mia M. , Subbiah Krishnaveni , Krop Esmeralda J. , Vermeulen Roel , Gapstur Susan M. 
Published: August 2019

Abstract
Although severe immune dysregulation is an established risk factor for B-cell non-Hodgkin lymphoma (B-NHL), the role of subtle immune perturbations is unclear. However, associations between plasma/serum immune markers and B-NHL in immunocompetent individuals suggest a role for more moderate immune dysregulation in lymphomagenesis. To further understand the associations of immune markers with B-NHL risk, we evaluated associations between these markers and subsequent B-NHL risk; and also examined potential lymphomagens as predictors of the markers. Among the eligible population of 32,704 cancer-free individuals in the Cancer Prevention Study-II Nutrition Cohort who donated a blood sample between 1998 and 2001, 273 B-NHL cases were identified during ~13 years of follow-up. Cases were incidence-density matched to cancer-free controls on age, race, and sex. Plasma level of soluble CD23 (sCD23), sCD27, sCD30, and CXCL13 were measured by ELISA at the Institute for Risk Assessment Sciences, Utrecht University. Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Associations between infectious, lifestyle, and demographic factors and B-activation marker level were examined using multivariable linear regression. We observed strong associations for all four markers with risk of B-NHL (per standard deviation increase in the biomarker: CXCL13: Risk Ratio (RR)=4.18, 95% confidence interval (CI): 2.46-7.11; CD23: RR=3.59, 95% CI: 2.50-5.18; CD27: RR=2.04, 95% CI: 1.48-2.81; CD30: RR=3.12, 95% CI: 2.01-4.84). The associations remained strong regardless of time between biomarker measurement and B-NHL diagnosis with the exception of sCD27 which was attenuated ≥8 years after biomarker measurement. We did not observe differences by major B-NHL subtype with the exception of a notably stronger association for sCD23 with chronic lymphocytic leukemia (CLL). Age was the strongest predictor of CXCL13 (p&lt;0.0001), sCD27 (p=0.0009), and sCD30 (p=0.0043) level, but was not associated with sCD23 (p=0.1018). Body mass index, smoking, and alcohol intake were not associated with any of the markers. However, two Epstein-Barr virus reactivation markers (early antigen and ZEBRA) were associated with sCD27 (p=0.004 and p=0.003 respectively).These varied risk factor associations and time-since-biomarker measurement patterns, suggest that there may be different roles in lymphomagenesis for different B-activation markers. Understanding these associations may help identify high risk individuals—and potential targets for early intervention for B-NHL.
Citation Format: Lauren R. Teras, Mia M. Gaudet, Krishnaveni Subbiah, Esmeralda J. Krop, Roel Vermeulen, Susan M. Gapstur. Clues to understanding the association between B-activation markers and the risk of B-cell non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 600.