TY - JOUR
T1 - Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma
T2 - univariate and functionally informed multivariate analyses
AU - Vermeulen, Roel
AU - Saberi Hosnijeh, Fatemeh
AU - Bodinier, Barbara
AU - Portengen, Lützen
AU - Liquet, Benoît
AU - Garrido-Manriquez, Javiera
AU - Lokhorst, Henk
AU - Bergdahl, Ingvar A.
AU - Kyrtopoulos, Soterios A.
AU - Johansson, Ann-Sofie
AU - Georgiadis, Panagiotis
AU - Melin, Beatrice
AU - Palli, Domenico
AU - Krogh, Vittorio
AU - Panico, Salvatore
AU - Sacerdote, Carlotta
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Castagné, Raphaële
AU - Chadeau-Hyam, Marc
AU - on behalf of the EnviroGenoMarkers Consortium Consortium members
AU - Botsivali, Maria
AU - Chatziioannou, Aristotelis
AU - Valavanis, Ioannis
AU - Kleinjans, Jos C. S.
AU - de Kok, Theo M. C. M.
AU - Keun, Hector C.
AU - Athersuch, Toby J.
AU - Kelly, Rachel
AU - Lenner, Per
AU - Hallmans, Goran
AU - Stephanou, Euripides G.
AU - Myridakis, Antonis
AU - Kogevinas, Manolis
AU - Fazzo, Lucia
AU - De Santis, Marco
AU - Comba, Pietro
AU - Bendinelli, Benedetta
AU - Kiviranta, Hannu
AU - Rantakokko, Panu
AU - Airaksinen, Riikka
AU - Ruokojarvi, Paivi
AU - Gilthorpe, Mark
AU - Fleming, Sarah
AU - Fleming, Thomas
AU - Tu, Yu-Kang
AU - Lundh, Thomas
AU - Chien, Kuo-Liong
AU - Chen, Wei J.
AU - Lee, Wen-Chung
AU - Kate Hsiao, Chuhsing
AU - Kuo, Po-Hsiu
AU - Hung, Hung
AU - Liao, Shu-Fen
N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - 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 before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) 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 model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF-α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10−7), TGF-α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein-3 (p = 1.36 × 10−4), macrophage inflammatory protein 1-alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor 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.
AB - 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 before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) 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 model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF-α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10−7), TGF-α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein-3 (p = 1.36 × 10−4), macrophage inflammatory protein 1-alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor 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.
KW - lymphoma
KW - multiple myeloma
KW - cytokine
KW - prospective cohort
KW - mixed-effect modeling
KW - multivariate models
KW - time to diagnosis
UR - http://www.scopus.com/inward/record.url?scp=85046006336&partnerID=8YFLogxK
U2 - 10.1002/ijc.31536
DO - 10.1002/ijc.31536
M3 - Article
C2 - 29667176
SN - 0020-7136
VL - 143
SP - 1335
EP - 1347
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 6
ER -