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.