Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma; univariate and functionally-informed multivariate analyses

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Title: Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma; univariate and functionally-informed multivariate analyses
Authors: Vermeulen, R
Saberi Hosnijeh, F
Bodinier, B
Portengen, L
Liquet, B
Garrido Manriquez, J
Lokhorst, H
Bergdahl, I
Kyrtopoulos, S
Johansson, A-S
Georgiadis, P
Melin, B
Palli, D
Krogh, V
Panico, S
Sacerdote, C
Tumino, R
Vineis, P
Castagne, RS
Chadeau, M
Item Type: Journal Article
Abstract: Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years prior to diagnosis (range, 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma) and matched controls. Linear mixed models, and Partial Least Square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes, and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed modelIrrespective of the model, our analyses identified associations linking blood lower immune markerslevels of and BCL incidence. In particular, we identified growth factors, and within that family, fibroblast growth factor-2 (FGF-2 , p=7.2x10 -4 ), ) and transforming growth factor alpha (TGF-α , p=6.5x10 -5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p=7.8x10 -7 ), TGF-α (p=4.08x10 -5 ), fractalkine (p=1.12x10 -3 ), monocyte chemotactic protein-3 (p=1.36x10 -4 ), macrophage inflammatory protein 1-alpha (p=4.6x10 -4 ), and vascular endothelial growth factor (p=4.23x10 -5 ). , and vascular endothelial growth factor (VEGF), to be consistently (and inversely) associated with MM incidence. Our results also provide d marginal support for already reported associations between chemokines and diffuse large B-Cell lymphoma (DLBCL) , and cytokines and chronic lymphocytic leukemia (CLL) . Case-only analyses showed that GM-CSF levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth-factors in the incidence of MM, and of chemokine and cytokine regulation in DLBCL and CLL.
Issue Date: 15-Sep-2018
Date of Acceptance: 19-Mar-2018
ISSN: 0020-7136
Publisher: Wiley
Start Page: 1335
End Page: 1347
Journal / Book Title: International Journal of Cancer
Volume: 143
Issue: 6
Copyright Statement: © 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: ‘Mechanomics’ PRC project grant 22184
Keywords: Science & Technology
Life Sciences & Biomedicine
multiple myeloma
prospective cohort
mixed-effect modeling
multivariate models
time to diagnosis
EnviroGenoMarkers Consortium Consortium members
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Online Publication Date: 2018-04-18
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine
Epidemiology, Public Health and Primary Care

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