Abstract 2880: A prospective study of 51 serum immune markers and risk of non-Hodgkin lymphoma.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), the etiologic relevance of subclinical immunologic effects is unclear. Few prospective studies have investigated the relationship between circulating immune markers and NHL, and those conducted to date have been limited in sample size, the number of evaluated analytes, or in their ability to examine markers of risk many years preceding disease diagnosis. To better understand this question, we conducted a nested case-control study investigating pre-diagnostic serum levels of 51 immune markers within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods: Fifty-one immune markers (including cytokines, chemokines, extracellular matrix proteins, growth factors and soluble products of immune activation) were measured in baseline serum from 301 NHL cases diagnosed 5+ years after blood collection (median 8.0 years, range 5.0-13.9) and 301 individually matched controls using Luminex bead-based assay panels. Odds ratios (ORs) and 95% confidence intervals (CIs) relating marker levels with NHL risk were computed using conditional logistic regression modeling. Results: We observed strong associations with NHL for elevated levels of several analytes: a pro-inflammatory marker, soluble tumor necrosis factor receptor 2 (sTNFRII; fourth quartile vs. first: OR 3.4, 95% CI 2.0-5.8; Ptrend = 5.9 x 10−6); a regulator of B-cell traffic, B-cell attracting chemokine 1 (BCA-1; 2.7, 1.7-4.2; Ptrend = 1.1 x 10−5); a regulator of angiogenesis, soluble vascular endothelial growth factor receptor 2 (sVEGFR2; 2.3, CI 1.4-3.9; Ptrend = 0.0005); and the pro-inflammation and apoptotic cytokine TNF-related apoptosis inducing ligand (TRAIL; 1.6, 1.0-2.5; Ptrend = 0.02). These associations remained significant in analyses of cases diagnosed 8-13 years after blood collection and, with the exception of TRAIL, following Bonferroni correction and simultaneous model adjustment. Conclusions: Our findings suggest that elevated levels of sTNFRII, BCA-1, sVEGFR2, and, possibly, TRAIL may reflect biologic processes contributing to lymphomagenesis. Additional research is needed to replicate these findings, identify cell sources of these markers, and elucidate the underlying biologic mechanisms. Citation Format: Mark P. Purdue, Jonathan N. Hofmann, Troy J. Kemp, Anil K. Chaturvedi, Qing Lan, Ju-Hyun Park, Ruth M. Pfeiffer, Allan Hildesheim, Ligia A. Pinto, Nathaniel Rothman. A prospective study of 51 serum immune markers and risk of non-Hodgkin lymphoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2880. doi:10.1158/1538-7445.AM2013-2880