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Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Computational Life Science Cluster (CLiC), Umeå University, 901 87 Umeå, Sweden.
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2016 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 8, 11065-11072 p.Article in journal (Refereed) Published
Abstract [en]

Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P = 0.008; OR = 1.58, 95 % CI = 1.13-2.22 and P = 0.017, OR = 1.63, 95 % CI = 1.09-2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P = 0.049; OR = 1.39, 95 % CI = 1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P = 0.024 and controls P = 0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2.

Place, publisher, year, edition, pages
2016. Vol. 37, no 8, 11065-11072 p.
Keyword [en]
Glioma, SNP, Serum EGFR, Serum ErbB2, Pre-diagnostic
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-126327DOI: 10.1007/s13277-015-4742-yISI: 000382672900107PubMedID: 26906551OAI: oai:DiVA.org:umu-126327DiVA: diva2:1043882
Available from: 2016-11-01 Created: 2016-10-03 Last updated: 2016-11-01Bibliographically approved

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Späth, FlorentinAndersson, UlrikaDahlin, Anna M.Grankvist, KjellBjörkblom, BennyWibom, CarlMelin, Beatrice
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