Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma

univariate and functionally informed multivariate analyses

on behalf of the EnviroGenoMarkers Consortium Consortium members

Research output: Contribution to journalArticle

7 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1335-1347
Number of pages13
JournalInternational Journal of Cancer
Issue number6
Publication statusPublished - 15 Sep 2018
Externally publishedYes

Bibliographical note

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.


  • lymphoma
  • multiple myeloma
  • cytokine
  • prospective cohort
  • mixed-effect modeling
  • multivariate models
  • time to diagnosis

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