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Pre‐diagnostic blood immune markers, incidence and progression of B‐cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses
Author(s) -
Vermeulen Roel,
Saberi Hosnijeh Fatemeh,
Bodinier Barbara,
Portengen Lützen,
Liquet Benoît,
GarridoManriquez Javiera,
Lokhorst Henk,
Bergdahl Ingvar A.,
Kyrtopoulos Soterios A.,
Johansson AnnSofie,
Georgiadis Panagiotis,
Melin Beatrice,
Palli Domenico,
Krogh Vittorio,
Panico Salvatore,
Sacerdote Carlotta,
Tumino Rosario,
Vineis Paolo,
Castagné Raphaële,
ChadeauHyam Marc,
Botsivali Maria,
Chatziioannou Aristotelis,
Valavanis Ioannis,
Kleinjans Jos C.S.,
de Kok Theo M.C.M.,
Keun Hector C.,
Athersuch Toby J.,
Kelly Rachel,
Lenner Per,
Hallmans Goran,
Stephanou Euripides G.,
Myridakis Antonis,
Kogevinas Manolis,
Fazzo Lucia,
De Santis Marco,
Comba Pietro,
Bendinelli Benedetta,
Kiviranta Hannu,
Rantakokko Panu,
Airaksinen Riikka,
Ruokojarvi Paivi,
Gilthorpe Mark,
Fleming Sarah,
Fleming Thomas,
Tu YuKang,
Lundh Thomas,
Chien KuoLiong,
Chen Wei J.,
Lee WenChung,
Kate Hsiao Chuhsing,
Kuo PoHsiu,
Hung Hung,
Liao ShuFen
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31536
Subject(s) - multiple myeloma , immunology , chemokine , medicine , immune system , chronic lymphocytic leukemia , prospective cohort study , gdf15 , oncology , biology , leukemia
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.