A prospective study of 67 serum immune and inflammation markers and risk of non-Hodgkin lymphoma

Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), the importance of subclinical immunologic effects is unclear. We compared baseline serum levels of 67 immune and inflammation markers between 301 patients with NHL diagnosed 51 years after blood collection and 301 control patients within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We observed associations with NHL for elevated B-cell-attracting chemokine 1 (BCA-1; fourth quartile vs first: odds ratio [OR], 2.7; 95% confidence interval [CI], 1.7-4.2; P_trend 5 1.0 3 10^-6), soluble tumor necrosis factor receptor 2 (sTNFR2; OR, 3.4; 95% CI, 2.0-5.8; P_trend 5 1.1 3 10^-6), and soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 2.3; 95% CI, 1.4-3.9; P_trend 5 .0005) that remained significant after Bonferroni correction, simultaneous model adjustment, and restriction to cases diagnosed 8 to 13 years after blood collection. Associations with other markers were observed, although none remained associated with NHL after adjustment for BCA-1, sTNFR2, and sVEGFR2. Our findings suggest that circulating BCA-1, sTNFR2, and sVEGFR2 are associated with NHL risk well in advance of diagnosis. Additional research is needed to replicate these findings and elucidate the underlying biologic mechanisms.