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Tumour Biol. 2016 Aug;37(8):11065-72. doi: 10.1007/s13277-015-4742-y. Epub 2016 Feb 23.

Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.

Author information

1
Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden. florentin.spaeth@umu.se.
2
Department of Oncology, Umeå University, 901 87, Umeå, Sweden. florentin.spaeth@umu.se.
3
Department of Radiation Sciences, Umeå University, 901 87, Umeå, Sweden.
4
Department of Oncology, Umeå University, 901 87, Umeå, Sweden.
5
Computational Life Science Cluster (CLiC), Umeå University, 901 87, Umeå, Sweden.
6
Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
7
Department of Informatics, University of Oslo, Oslo, Norway.
8
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
9
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
10
Department of Medical Biosciences, Clinical Chemistry, Umeå University, 901 85, Umeå, Sweden.
11
Department of Chemistry, Umeå University, 901 87, Umeå, Sweden.

Abstract

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.

KEYWORDS:

Glioma; Pre‐diagnostic; SNP; Serum EGFR; Serum ErbB2

PMID:
26906551
PMCID:
PMC4999462
DOI:
10.1007/s13277-015-4742-y
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Compliance with ethical standardsFundingThis study was supported by Acta Oncologica foundation through the Royal Swedish Academy of Science (BM salary), The Swedish Research Council, Swedish Cancer foundation, Northern Sweden Cancer foundation, Umeå University Young investigator reward, and Umeå Hospital cutting edge grant.Conflicts of interestNoneEthical approvalAll procedures involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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