Abstract 5074: Elevated serum free light chains and risk of non-Hodgkin lymphoma and the subtype follicular lymphoma in a prospective cohort study
Authors: Hu Wei , Landgren Ola , Bassig Bryan , Purdue Mark , Engels Eric , Lan Qing , Rothman Nathaniel 
Published: May 2015

Abstract
Background: Serum free light chains (FLC) are plausible biomarkers associated with risks of Hodgkin and non-Hodgkin lymphoma (NHL) or its subtypes.
Methods: We investigated the relationship between free light chains and the risks of non-Hodgkin lymphoma (NHL) with a particular focus on two major subtypes - diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) using samples from the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Kappa and lambda free light chains were analyzed in 292 incident NHL cases [including 62 DLBCL, 45 FL and 122 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) cases] and 292 controls individually-matched to cases on age, sex, race, study center, and date of baseline blood draw. Conditional logistic regression was performed to compute the odds ratios (ORs) and 95% confidence intervals (CIs). Impact of follow-up time from blood collection to case diagnosis was evaluated by stratifying on 1-4 and 5-10 years of follow-up in cases and the matched controls.
Results: Elevated kappa and/or lambda FLC above the upper limit of normal (ULN) were found to be significantly associated with risks of overall NHL [OR(95% CI): 1.74(1.04-2.90)]. Further analysis on risk of NHL by FLC divided into quartiles based on the distribution in controls showed a stronger dose-response relationship with lambda FLC (ptrend=0.034, adjusted for kappa FLC) than kappa FLC (ptrend=0.15, adjusted for lambda FLC). Lambda FLC also showed a stronger relationship with risk of NHL in 5-10 follow-up years [OR(95% CI): 3.11(1.26-7.66) and 3.58(1.36-9.40) for the second highest and the highest vs. lowest quartile, respectively, ptrend=0.0097, adjusted for kappa FLC] in contrast to 1-4 years (ptrend=0.95, adjusted for kappa FLC). Though the clinical definition of abnormal level did not show an association with FL, likely due to small numbers, there was a strong dose-response relationship between quartiles of lambda FLC and risk of FL [OR(95% CI) for highest vs. lowest quartile: 14.51(2.58-81.54), ptrend=0.0054]. No significant associations were observed between FLC and DLBCL. We also found that elevated kappa FLC was associated with CLL/SLL [OR(95% CI) for highest vs. lowest quartile: 1.92(0.85-4.35), ptrend=0.019], consistent with findings from a previous report from this study.
Conclusion: These findings suggest that immune activation precedes development of clinically apparent FL.
Citation Format: Wei Hu, Ola Landgren, Bryan Bassig, Mark Purdue, Eric Engels, Qing Lan, Nathaniel Rothman. Elevated serum free light chains and risk of non-Hodgkin lymphoma and the subtype follicular lymphoma in a prospective cohort study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5074. doi:10.1158/1538-7445.AM2014-5074