Pre‐diagnostic levels of sVEGFR2, sTNFR2, sIL‐2Rα and sIL‐6R are associated with glioma risk: A nested case–control study of repeated samples

Abstract

No strong aetiological factors have been established for glioma aside from genetic mutations and variants, ionising radiation and an inverse relationship with asthmas and allergies. Our aim was to investigate the association between pre‐diagnostic immune protein levels and glioma risk. We conducted a case–control study nested in the Northern Sweden Health and Disease Study cohort. We analysed 133 glioma cases and 133 control subjects matched by age, sex and date of blood donation. ELISA or Luminex bead‐based multiplex assays were used to measure plasma levels of 19 proteins. Conditional logistic regression models were used to estimate the odds ratios and 95% CIs. To further model the protein trajectories over time, the linear mixed‐effects models were conducted. We found that the levels of sVEGFR2, sTNFR2, sIL‐2Rα and sIL‐6R were associated with glioma risk. After adjusting for the time between blood sample collection and glioma diagnosis, the odds ratios were 1.72 (95% CI = 1.01–2.93), 1.48 (95% CI = 1.01–2.16) and 1.90 (95% CI = 1.14–3.17) for sTNFR2, sIL‐2Rα and sIL‐6R, respectively. The trajectory of sVEGFR2 concentrations over time was different between cases and controls (p‐value = 0.031), increasing for cases (0.8% per year) and constant for controls. Our findings suggest these proteins play important roles in gliomagenesis.

Elevation of circulating TNF receptor 2 in cancer: A systematic meta-analysis for its potential as a diagnostic cancer biomarker

“…After excluding 2,787 animal studies, 4,089 in vitro studies, 2,642 secondary source articles, and 1,173 conference articles, 3,942 full-length articles were assessed for their eligibility. After applying the inclusion and exclusion criteria, 44 studies ( 53 – 97 ) were included in this meta-analysis. PRISMA Flow chart ( Figure 1 ) shows the number of studies searched and selected.…”

Pre-diagnostic blood biomarkers for adult glioma

“…Although, this relationship was not identified in all glioma cases as evidenced in other studies ( 11 , 12 ). Increased circulating vascular endothelial growth factor (VEGF) was found to be associated with pre-diagnostic glioma (OR=1.46, 95% CI=1.18-1.82) in the JSB, whilst two other studies did not find the same relationship within the Department of Defense Serum Repository (DoDSR) and Northern Sweden and Disease Study cohort (NSHDS) cohorts ( 8 , 12 , 13 ). Increased levels of soluble vascular endothelial growth factor receptor 2 (sVEGFR2) was found to be associated with increased glioma risk (OR=2.44, 95% CI=1.29-4.61) ( 13 ).…”

“…Increased circulating vascular endothelial growth factor (VEGF) was found to be associated with pre-diagnostic glioma (OR=1.46, 95% CI=1.18-1.82) in the JSB, whilst two other studies did not find the same relationship within the Department of Defense Serum Repository (DoDSR) and Northern Sweden and Disease Study cohort (NSHDS) cohorts ( 8 , 12 , 13 ). Increased levels of soluble vascular endothelial growth factor receptor 2 (sVEGFR2) was found to be associated with increased glioma risk (OR=2.44, 95% CI=1.29-4.61) ( 13 ). No associations were found between placental growth factor (PLGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGFβ1), fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα) levels and pre-diagnostic glioma patients ( 8 , 12 , 13 ).…”

“…Increased levels of soluble vascular endothelial growth factor receptor 2 (sVEGFR2) was found to be associated with increased glioma risk (OR=2.44, 95% CI=1.29-4.61) ( 13 ). No associations were found between placental growth factor (PLGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGFβ1), fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα) levels and pre-diagnostic glioma patients ( 8 , 12 , 13 ).…”

“…Conversely, Calboli and colleagues did not find an association between elevated IgE levels and risk of glioma, but there was suggestive evidence of an association in the Nurses’ Health Study, Women’s Health Study (WHS), HPFS, and Physicians’ Health Study (PHS) cohort ( 27 ). A receptor for IgE, soluble cluster of differentiation 23 (sCD23), was also investigated but no relationship was found with pre-diagnostic glioma in the JSB and NSHDS cohort ( 12 , 13 ).…”