@article{3056344, title = "Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development", author = "Saberi Hosnijeh, F. and Kolijn, P.M. and Casabonne, D. and Nieters, A. and Solans, M. and Naudin, S. and Ferrari, P. and Mckay, J.D. and Weiderpass, E. and Perduca, V. and Besson, C. and Mancini, F.R. and Masala, G. and Krogh, V. and Ricceri, F. and Huerta, J.M. and Petrova, D. and Sala, N. and Trichopoulou, A. and Karakatsani, A. and La Vecchia, C. and Kaaks, R. and Canzian, F. and Aune, D. and Boeing, H. and Schulze, M.B. and Perez-Cornago, A. and Langerak, A.W. and van der Velden, V.H.J. and Vermeulen, R.", journal = "Scientific Reports", year = "2020", volume = "10", number = "1", publisher = "Institute of Geographic Sciences and Natural Resources Research", issn = "2045-2322", doi = "10.1038/s41598-020-70790-9", keywords = "biological marker; CXCL13 chemokine; CXCL13 protein, human; leukocyte antigen, B lymphocyte; body mass; case control study; chronic lymphatic leukemia; cohort analysis; diffuse large B cell lymphoma; exercise; female; follicular lymphoma; human; immunology; lifestyle; lymphocyte activation; male; physiology; prospective study, Antigens, CD; B-Lymphocytes; Biomarkers; Body Mass Index; Case-Control Studies; Chemokine CXCL13; Cohort Studies; Exercise; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Life Style; Lymphocyte Activation; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Male; Prospective Studies", abstract = "Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case–control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors. © 2020, The Author(s)." }